Sulfonamide and carboxamide derivatives and drugs containing the same as the active ingredient

ABSTRACT

The sulfonamide or carboamide derivatives of the formula (I) and a pharmaceutical composition which comprise them as an active ingredient:                    
     (wherein A ring, B ring is carbocyclic ring, heterocyclic ring; Z 1  is —COR 1 , —CH═CH—COR 1  etc.; Z 2  is H, alkyl etc.; Z 3  is single bond, alkylene; Z 4  is SO 2 , CO; Z 5  is alkyl, phenyl, heterocyclic ring etc.; R 2  is CONR 8 , O, S, NZ 6 , Z 7 -alkylene, alkylene etc.; R 3  is H, alkyl, halogen, CF 3  etc.; R 4  is H, (substituted) alkyl etc.; n, t is  1-4 ). 
     The compounds of the formula (I) can bind to receptors of PGE 2  and show antagonistic activity against the action thereof or agonistic activity. Therefore, they are considered to be useful as medicine for inhibition of uterine contraction, analgesics, antidiarrheals, sleep inducers, medicine for increase of vesical capacity or medicine for uterine contraction, cathartic, suppression of gastric acid secretion, antihypertensive or diuretic agents.

This application is a 371 of PCT/JP97/04593, filed Dec. 12, 1997.

FIELD OF TECHNOLOGY

This invention relates to sulfonamide and carboamide derivatives. Moreparticularly, thisinvention relates to

(1) the compounds of the formula (I)

(wherein all symbols are as hereinafter defined.),

(2) processes for preparing them and

(3) Prostaglandin E₂ (abbreviated as PGE₂) antagonists or agonists whichcomprise them as an active ingredient.

BACKGROUND

PGE₂ has been known as metabolite in the arachidonate cascade. It hasbeen known that PGE₂ causes uterine contraction, induction of pain,promotion of digestive peristalsis, awakening effect, vesicacontraction, suppression of gastric acid secretion or reduction of bloodpressure etc. The PGE₂antagonist or PGE₂agonist is expected to show thefollowing actions.

To antagonize against PGE₂ means to suppress the effects abovementioned, so such an activity is linked to inhibition of uterinecontraction, analgesic action, inhibition of digestive peristalsis,induction of sleep or increase of vesical capacity. Therefore, PGE₂antagonists are considered to be useful for the prevention of abortion,as analgesics, as antidiarrheals, as sleep inducers or as agents fortreating pollakiuria.

To show PGE₂ agonistic activity means to promote the effects abovementioned, so such an activity is linked to uterine contraction,promotion of digestive peristalsis, suppression of gastric acidsecretion or reduction of blood pressure or diuresis. Therefore, PGE₂agonists are considered to be useful as abortifacient, cathartic,antiulcer, anti-gastritis, antihypertensive or diuretic agents.

A lot of PGE₂ agonists including PGE₂ itself etc. have been known, butonly a few compounds (PGE₂ antagonists) possessing the inhibition ofactivity of PGE₂ by antagonizing against PGE₂ have been known.

For example, the patent applications relating to PGE antagonists are asfollows:

In the specification of WO-96/03380, it is disclosed that the compoundsof the formula (A)

(wherein A is phenyl which may be substituted etc., B is ring systemwhich may be substituted, D is ring system which may be substituted,R^(1A) is carboxyl etc., R^(2A) is H, C1-6 alkyl etc., R^(3A) is H, C1-4alkyl, R^(4A) is H, C1-4 alkyl (as excerpt).) are active as PGEantagonists.

In the specification of WO-96/06822, it is disclosed that the compoundsof the formula (B)

(wherein A is ring system which may be substituted, B is hetero arylring which may be substituted or phenyl which may be substituted, D isring system which may be substituted, X^(B) is (CHR^(4B))_(n) B or(CHR^(4B))_(p)CR^(4B=CR) ^(4B) (CHR^(4B))_(q), R^(1B) is carboxyl etc.,R^(3B) is H, C1-4 alkyl R^(4B) is H, C1-4 alkyl (as excerpt).)

are active as PGE antagonists.

In the specification of WO-96/11 902, it is disclosed that the compoundsof the formula (C)

(wherein A, B and D are various ring systems, R^(1C) is carboxyl etc.,R^(3C) is H, C1-4 alkyl, Z is —(CH(R^(5C)))_(m) etc. (as excerpt))

are active as PGE antagonists.

On the other hand, some compounds having a similar structure to thepresent invention compounds have been known.

For example, the following compound is described in Justus Liebigs Ann.Chem. (1909), 367, 133.

(wherein R^(D) is H or ethyl.)

The following compound is described in Khim. Geterotsikl. Soedin (1974),(6), 760.

(wherein R^(E) is phenethyl, benzyl, hexadecyl, decyl, nonyl, butyl,propyl, ethyl, methyl.)

The following compound is described in Khim. Geterotsikl. Soedin (1972),(10), 1341.

(wherein R^(F) is nitro or methoxy.)

The following compound is described in Khim. Geterotsikl. Soedin (1972),(5), 616.

The following compound is described in Khim. Geterotsikl. Soedin (1976),(5), 641.

The following compound is described in Khim. Geterotsikl. Soedin (1971),(7), 1028.

The following compound is described in Khim. Geterotsikl. Soedin (1970),(12), 1597.

(wherein each R^(K) is Br or Cl.)

The compounds of the formula (A), (B) and (C) in the related artspossess the same pharmacological activity as the present inventioncompounds. But there is a difference in structure as follows: Thepresent invention compounds have sulfonamide or carboamide as anessential element in their structure. On the other hand, the compoundsdescribed in such related arts have ether or alkylene in thecorresponding part. So, it is not easy to predict the present inventioncompounds from the structure of these related arts.

In addition, the compounds of the formula (D) to (K) relate to the studyfor synthesis only. In these literature, there is no description onpharmacological activity. The carboxyl group in such compounds isconnected at the ortho position, so the present invention compounds aredifferent from such compounds in structure. Therefore, it is not easy topredict the present invention from such compounds possessing thedifferent activity and structure.

THE DISCLOSURE OF THE INVENTION

The present invention relates to

(1) sulfonamide or carboamide derivatives of the formula (I)

(wherein

each, independently, is C5-15 carbocyclic ring or 5-7 memberedheterocyclic ring containing one or two oxygen, sulfur or nitrogenatom(s),

Z¹ is

—COR¹,

—C1-4 alkylene-COR¹,

—CH═CH—COR¹,

—C≡COR¹, or

—O—C1-3 alkylene-COR¹

(wherein R¹ is hydroxy, C1-4 alkoxy or formula

NR⁶R⁷

(wherein R⁶ and R⁷ each, independently, is H or C1-4 alkyl.).), or —C1-5alkylene-OH,

Z² is H, C1-4 alkyl, C1-4 alkoxy, nitro, halogen, trifluoromethyl,trifluoromethoxy, hydroxy or COR¹ (wherein R¹ is as hereinbeforedefined.),

Z³ is single bond or C1-4 alkylene,

Z⁴ is SO₂ or CO,

Z⁵ is

(1) C1-8 alkyl, C2-8 alkenyl, or C2-8 alkynyl,

(2) phenyl, C3-7 cycloalkyl, or 5-7 membered heterocyclic ringcontaining one or two oxygen, sulfur or nitrogen atom(s), or

(3) C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl substituted by phenyl orC3-7 cycloalkyl

(phenyl, C3-7 cycloalkyl, and 5-7 membered heterocyclic ring containingone or two oxygen, sulfur or nitrogen atom(s) mentioned in the above (2)and (3) may be substituted by 1-5 of R⁵ (wherein R⁵ (if two or more R⁵,each independently) is H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio,nitro, halogen, tifluoromethyl, trifluoromethoxy or hydroxy.).),

R² is

CONR⁸,

NR⁸CO,

CONR⁸-C1-4 alkylene,

C1-4 alkylene-CONR⁸,

NR⁸CO-C1-4 alkylene,

C1-4 alkylene-NR⁸CO,

C1-3 alkylene-CONR⁸-C1-3 alkylene, or

C1-3 alkylene-NR⁸CO-C1-3 alkylene

(wherein each R⁸ is H or C1-4 alkyl.), O, S, NZ⁶

(wherein Z⁶ is H or C1-4 alkyl.),

Z⁷-C1-4 alkylene,

C1-4 alkylene-Z⁷, or

C1-3 alkylene-Z⁷-C1-3 alkylene

(wherein each Z⁷ is O, S or NZ⁶ (wherein Z⁶ is as hereinbeforedefined.).),

NZ⁶SO₂ (wherein Z⁶ is as hereinbefore defined),

CO,

CO-C1-4 alkylene,

C1-4 alkylene-CO,

C1-3 alkylene-CO-C1-3 alkylene,

C2-4 alkylene,

C2-4 alkenylene, or

C2-4 alkynylene,

R³ is H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, nitro, halogen,trifluoromethyl, trifluoromethoxy, hydroxy or hydroxymethyl,

R⁴ is

(1) H,

(2) C1-8 alkyl, C2-8 alkenyl, or C2-8 alkynyl,

(3) C1-6 alkyl substituted by one or two substituent(s) selected fromthe group consisting of COOZ⁸, CONZ⁹Z¹⁰, and OZ⁸ (wherein Z⁸, Z⁹ and Z¹⁰each, independently, is H or C1-4 alkyl.) and C1-4 alkoxy-C1-4 alkoxy,

(4) C3-7 cycloalkyl, or

(5) C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl substituted by phenyl orC3-7 cycloalkyl

(phenyl and C3-7 cycloalkyl mentioned in the above (4) and (5) may besubstituted by 1-5 of R⁵ (wherein R⁵ is as hereinbefore defined.).), andn and t each, independently, is an integer of 1-4,

with the proviso that (1) R² and Z³ should be connected at the 1- or2-position of

 and (2) when

 is a benzene ring and (Z²)t is other than COR¹, Z¹ should be connectedat the 3- or 4-position of the benzene ring.), or a non-toxic saltthereof,

(2) processes for preparing them and

(3) PGE₂ antagonists or agonists which comprise them as an activeingredient.

DETAILED DESCRIPTION OF THE INVENTION

In the formula (I), C1-4 alkyl in Z⁵ and R⁴ and C1-4 alkyl representedby Z², Z⁶, Z⁸, Z⁹, Z¹⁰, R⁶, R⁷ and R⁸ means methyl, ethyl, propyl, butyland isomer thereof.

In the formula (I), C1-6 alkyl in R⁴ and C1-6 alkyl represented by R³and R⁵ means methyl, ethyl, propyl, butyl, pentyl, hexyl and isomerthereof.

In the formula (I), C1-8 alkyl represented by Z⁵ and R⁴ means methyl,ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and isomer thereof.

In the formula (I), C2-4 alkenyl in Z⁵ and R⁴ means vinyl, propenyl,butenyl and isomer thereof.

In the formula (I), C2-8 alkenyl represented by Z⁵ and R⁴ means C2-8alkyl having 1-3 of double bond and, for example, vinyl, propenyl,butenyl, pentenyl, hexenyl, heptenyl, octenyl etc. and isomer thereof.

In the formula (I), C2-4 alkynyl in Z⁵ and R⁴ means ethynyl, propynyl,butynyl and isomer thereof.

In the formula (I), C2-8 alkynyl represented by Z⁵ and R⁴ means C2-8alkyl having 1-3 of triple bond and, for example, ethynyl, propynyl,butynyl, pentynyl, hexynyl, heptynyl, octynyl etc. and isomer thereof.

In the formula (I), C1-4 alkoxy in R⁴ and C1-4 alkoxy represented by Z²and R¹ means methoxy, ethoxy, propoxy, butoxy and isomer thereof.

In the formula (I), C1-6 alkoxy represented by R³ and R⁵ means methoxy,ethoxy, propoxy, butoxy, pentyloxy, hexyloxy and isomer thereof.

In the formula (I), C1-6 alkylthio represented by R³ and R⁵ meansmethylthio, ethylthio, propylthio, butylthio, pentylthio, hexylthio andisomer thereof.

In the formula (I), C1-3 alkylene in Z¹ and R² means methylene,ethylene, trimethylene and isomer thereof.

In the formula (I), C1-4 alkylene in Z¹ and R² and C1-4 alkylenerepresented by Z³ means methylene, ethylene, trimethylene,tetramethylene and isomer thereof.

In the formula (I), C1-5 alkylene in Z¹ means methylene, ethylene,trimethylene, tetramethylene, pentamethylene and isomer thereof.

In the formula (I), C2-4 alkylene represented by R² means ethylene,trimethylene, tetramethylene and isomer thereof.

In the formula (I), C2-4 alkenylene represented by R² means vinylene,propenylene, butenylene and isomer thereof.

In the formula (I), C2-4 alkynylene represented by R² means ethynylene,propynylene, butynylene and isomer thereof.

In the formula (I), C3-7 cycloalkyl in Z⁵ and R⁴ and C3-7 cycloalkylrepresented by Z⁵ and R⁴ means cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl.

In the formula (I), C5-15 carbocyclic ring represented by

means mono-, bi- or tri-ring of C5-15 carbocyclic aryl, or partially orfully saturated ring thereof.

For example, C5-15 carbocyclic aryl includes benzene, pentalene, indene,naphthalene, azulene, fluorene, anthracene etc. Partially or fullysaturated ring thereof includes the above mentioned ring which ispartially or fully saturated.

As for C5-15 carbocyclic ring, preferably, mono- or bi-ring of C5-10carbocyclic aryl and the mentioned C5-7 cycloalkyl is listed, and morepreferably, benzene, naphthalene, cyclopentyl, cyclohexyl orcycloheptyl.

In the formula (I), 5-7 membered heterocyclic ring containing one or twooxygen, sulfur or nitrogen atom(s) represented by

and Z⁵ means 5-7 membered heterocyclic aryl ring containing one or twooxygen, sulfur or nitrogen atom(s) or partially or fully saturated ringthereof.

5-7 membered heterocyclic aryl ring containing one or two oxygen, sulfuror nitrogen atom(s) includes pyrrole, imidazole, pyrazole, pyridine,pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran,oxepine, oxazepine, thiophen, thiain (thiopyran), thiepine, oxazole,isoxazole, thiazole, isothiazole, oxadiazole, oxadiazine, oxazepine,oxadiazepine, thiadiazole, thiadiazine, thiadiazepine etc.

5-7 membered heterocyclic aryl ring containing one or two oxygen, sulfuror nitrogen atom(s) which is partially or fully saturated includespyrroline, pyrrolidine, imidazoline, imidazolidine, pyrazoline,pyrazolidine, piperidine, piperazine, tetrahydropyrimidine,tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran,tetrahydropyran, dihydrothiophen, tetrahydrothiophen, dihydrothiain(dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran),dihydroxazole, tetrahydroxazole, dihydroisoxazole, tetrahydroisoxazole,dihydrothiazole, tetrahydrothiazole, dihydroisothiazole,tetrahydroisothiazole, morpholine, thiomorpholine etc.

In the formula (I), halogen represented by Z², R³ and R⁵ means chlorine,bromine, fluorine and iodine.

In the formula (I), as for Z³ which represents single bond or C1-4alkylene, preferably, single bond or methylene is listed and morepreferably, single bond.

In the formula (I), as for Z⁴ which represents SO₂ or CO, preferably SO₂is listed.

In the formula (I), as for R⁴, preferably, every group is listed andmore preferably, group other than hydrogen.

Unless otherwise specified, all isomers are included in the invention.For example, alkyl, alkylene and alkenylene includes straight-chain orbranched-chain ones. Double bond in alkenylene include structure ofconfigurations E, Z and EZ mixtures. Isomers generated by asymmetriccarbon(s) e.g. branched alkyl are also included in the presentinvention.

In the compounds of the formula (I) of the present invention, thecompounds wherein

is C5-15 carbocyclic ring and Z⁵ is C1-8 alkyl, C2-8 alkenyl, C2-8alkynyl, or group containing phenyl or C3-7 cycloalkyl (each ring may besubstituted.) are preferable. The compounds wherein

is mono- or bi-ring of C5-10 carbocyclic aryl and C5-7 cycloalkyl and Z⁵is the above mentioned group are more preferable.

The compounds wherein at least one of

and Z⁵ is 5-7 membered heterocyclic ring containing one or two oxygen,sulfur or nitrogen atom(s) (each ring may be substituted.) are alsopreferable. Such compounds include, for example, the compounds wherein(1)

is C5-15 carbocyclic ring and Z⁵ is 5-7 membered heterocyclic ringcontaining one or two oxygen, sulfur or nitrogen atom(s) or (2) one of

is 5-7 membered heterocyclic ring containing one or two oxygen, sulfuror nitrogen atom(s) and the other is C5-15 carbocyclic ring. Thecompounds wherein carbocyclic ring represented by

and/or

in case of the above (1) and (2) is mono- or bi-ring of C5-10carbocyclic aryl and C5-7 cycloalkyl are more preferable.

In the compounds of the formula (I) of the present invention, concreteand preferable compounds include the compounds described in the Examplesand corresponding esters and amides.

[Salt]

The compounds of the present invention of the formula (I) may beconverted into the corresponding salts by methods known per se.Non-toxic and water-soluble salts are preferable. Suitable salts, forexample, are as follows: salts of alkali metals (potassium, sodiumetc.), salts of alkaline earth metals (calcium, magnesium etc.),ammonium salts, salts of pharmaceutically acceptable organic amines(tetramethylammonium, triethylamine, methylamine, dimethylamine,cyclopentylamine, benzylamine, phenethylamine, piperidine,monoethanolamine, diethanolamine, tris(hydroxymethyl)aminomethane,lysine, arginine, N-methyl-D-glucamine etc.).

The Method of the Preparation for the Present Invention Compounds

The compounds of the formula (I) of the present invention may beprepared by the method described in the following, the method describedin the Examples as hereinafter or known methods.

(1) In the compounds of the formula (I) of the present invention, thecarboxylic acid compounds of the formula (Ia)

(wherein Z^(1a) and Z^(2a) are as Z¹ and Z², respectively, with theproviso that at least one of them is COOH or a group containing COOH,and the other symbols are as hereinbefore defined.)

may be prepared from the ester compound of the formula (Ib)

(wherein Z^(1b) and Z^(2b) are as Z¹ and Z², respectively, with theproviso that at least one of them is COR^(1b) or a group containingCOR^(1b) (wherein R^(1b) is C1-4 alkoxy or methoxymethoxy (abbreviatedas OMOM.).),

R^(3b), R^(4b) and Z^(5b) are as R³, R⁴ and Z⁵, respectively, with theproviso when R³, R⁴ or R⁵ in Z⁵ is COOH or hydroxy, or a groupcontaining COOH or hydroxy, each COOH and hydroxy is protected by aprotecting group which is removable under an acidic, neutral or alkalinecondition, and the other symbols are as hereinbefore defined.)

by hydrolysis under an alkaline, acidic or neutral condition, ifnecessary, followed by hydrolysis under the different condition.

The removal of a protecting group by hydrolysis under an alkaline,acidic or neutral condition is a well-known reaction as hereinafterdescribed.

(2) In the compounds of the formula (I) of the present invention, theester compounds of the formula (Ic)

(wherein Z^(1c) and Z^(2c) are as Z¹ and Z², respectively, with theproviso that at least one of them is COR^(1c) or a group containingCOR^(1c) (wherein R^(1c) is C1-4 alkoxy.) and the other symbols are ashereinbefore defined.)

may be prepared from the compound of the formula (Ia) by esterification.

Esterification is well known, it may be carried out, for example;

(a) by the method using diazoalkane,

(b) by the method using alkyl halide,

(c) by the method using dimethylformamide (DMF)-dialkyl acetal or

(d) by the method reacting corresponding alkanol etc.

Concrete description of the methods described above are as follows:

(a) The method using diazoalkane may be carried out, for example, usingcorresponding diazoalkane in an organic solvent (diethylether, ethylacetate, methylene chloride, acetone, methanol or ethanol etc.) at−10˜40° C.

(b) The method using alkyl halide may be carried out, for example, in anorganic solvent (acetone, DMF, dimethylsufoxide (DMSO) etc.) in thepresence of base (potassium carbonate, sodium carbonate, potassiumhydrogen carbonate, sodium hydrogen carbonate, calcium oxide etc.) usingcorresponding alkyl halide at −10˜40° C.

(c) The method using DMF-dialkyl acetal may be carried out, for example,in an organic solvent (benzene, toluene etc.) using correspondingDMF-dialkyl acetal at −10˜40° C.

(d) The method of reacting corresponding alkanol may be carried out, forexample, in corresponding alkanol (HR^(1c) (R^(1c) is as hereinbeforedefined.)) using acid (HCl, sulfuric acid, p-toluene sulfonic acid,hydrochloride gas etc.) or condensing agents (DCC, pivaloyl halide, arylsulfonyl halide, alkyl sulfonyl halide etc.) at 0˜40° C.

Of course, an organic solvent (tetrahydrofuran, methylene chloride etc.)which does not relate to the reaction may be added in theseesterification.

(3) In the compounds of the formula (I) of the present invention, theamide compounds of the formula (Id)

(wherein Z^(1d) and Z^(2d) are as Z¹ and Z², respectively, with theproviso that at least one of them is COR^(1d) or a group containingCOR^(1d) (wherein R^(1d) is NR⁶R⁷ (wherein all symbols are ashereinbefore defined.), and the other symbols are as hereinbeforedefined.) may be prepared by reacting the compound of the formula (Ia)with the compound of the formula (III)

HNR⁶R⁷  (III)

(wherein all symbols are as hereinbefore defined.) to form the amidebond.

Reaction to form amide-bond is well known, it may be carried out, forexample, in an organic solvent (THF, methylene chloride, benzene,acetone, acetonitrile etc.), in the presence or absence of tertiaryamine (dimethylaminopyridine, pyridine, triethylamine etc.) using acondensing agent (EDC or DCC etc.) at 0˜50° C.

(4) In the compounds of the formula (I) of the present invention, thealcohol compounds of the formula (Ie)

(wherein Z^(1e) is C1-5 alkylene-OH, and the other symbols are ashereinbefore defined.)

may be prepared by the reduction of the compound of the formula (If)

(wherein Z^(1f) is COOY^(f) or C1-4 alkylene-COOY^(f) (wherein Y^(f) isC1-4 alkyl.), and the other symbols are as hereinbefore defined.).

The reductive reaction is known, and for example, this reaction may becarried out in the presence of organic solvent (THF, methylene chloride,diethylether, lower alkanol etc.) using lithium aluminum hydride (LAH)or diisobutyl aluminum hydride (DIBAL) at −78° C. to room temperature.

(5) In the compounds of the formula (Ib), wherein R² is CONR⁸, C1-4alkylene-CONR⁸, CONR⁸-C1-4 alkylene, C1-3 alkylene-CONR⁸-C1-3 alkylene,(wherein all symbols are as hereinbefore defined.), i.e. the compoundsof the formula (Ib-1)

(wherein R²⁰ is CONR⁸, C1-4 alkylene-CONR⁸, CONR⁸-C1-4 alkylene, C1-3alkylene-CONR⁸-C1-3 alkylene, (wherein all symbols are as hereinbeforedefined.), and the other symbols are as hereinbefore defined.)

may be prepared by reacting the compound of the formula (IV)

(wherein R²⁰⁰ is single bond or C1-4 alkylene, and the other symbols areas hereinbefore defined.)

with the compound of the formula (V)

(wherein R²⁰¹ is single bond or C1-4 alkylene, and the other symbols areas hereinbefore defined.) to form amide bond.

Reaction to form amide bond may be carried out as the method describedin the said (3).

(6) In the compounds of the formula (Ib), wherein R² is NR⁸CO, C1-4alkylene-NR⁸CO, NR⁸CO-C1-4 alkylene, C1-3 alkylene-NR⁸CO-C1-3 alkylene(wherein all symbols are as hereinbefore defined.), i.e. the compoundsof the formula (Ib-2)

(wherein R²¹ is NR⁸CO, C1-4 alkylene-NR⁸CO, NR⁸CO-C1-4 alkylene, C1-3alkylene-NR⁸CO-C1-3 alkylene (wherein all symbols are as hereinbeforedefined.), and the other symbols are as hereinbefore defined.)

may be prepared by reacting the compound of the formula (VI)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (VIl)

(wherein all symbols are as hereinbefore defined.)

to form amide bond.

Reaction to form amide bond may be carried out as the method describedin the said (3).

(7) In the compounds of the formula (Ib), wherein R² is O, S, NZ⁶,Z⁷-C1-4 alkylene, C1-4 alkylene-N⁷ or C1-3 alkylene N⁷-C1-3 alkylene(wherein all symbols are as hereinbefore defined.), i.e. the compoundsof the formula (Ib-3)

(wherein R²² is O, S, NZ⁶, Z⁷-C1-4 alkylene, C1-4 alkylene-N⁷ or C1-3alkylene-N⁷-C1-3 alkylene (wherein all symbols are as hereinbeforedefined.).)

may be prepared by reacting the compound of the formula (VIII)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (IX)

X—Z⁴—Z^(5b)  (IX)

(wherein X is halogen and the other symbols are as hereinbeforedefined.) to form sulfonamide bond or carboamide bond.

Reactions to form sulfonamide bond or carboamide bond may be carriedout, for example, in an organic solvent (THF, methylene chloride,benzene, acetone, acetonitrile etc.), in the presence or absence oftertiary amine (dimethylaminopyridine, pyridine, triethylamine etc.) at0˜50° C.

(8) In the compounds of the formula (Ib), wherein R² is NZ⁶-C1-4alkylene, C1-4 alkylene-NZ⁶ or C1-3 alkylene-NZ⁶-C1-3 alkylene (whereinall symbols are as hereinbefore defined.), i.e. the compounds of theformula (Ib-4)

(wherein R²³ is NZ⁶-C1-4 alkylene, C1-4 alkylene-NZ⁶ or C1-3alkylene-NZ⁶-C1-3 alkylene (wherein all symbols are as hereinbeforedefined.) and the other symbols are as hereinbefore defined.)

may be prepared by

(a) reacting (reductive amination) the compound of the formula (VI-a)

(wherein R²³⁰ is single bond or C1-4 alkylene, and the other symbols areas hereinbefore defined.)

with the compound of the formula (VII-a)

 (wherein R²³¹ is single bond or C1-3 alkylene, and the other symbolsare as hereinbefore defined.) or

(b) reacting (reductive amination) the compound of the formula (VI-b)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (VII-b)

(wherein all symbols are as hereinbefore defined.).

The reaction of reductive amination described in the above (a) and (b)may carried out, for example, in organic solvent (methanol etc.), in anacidic condition, using a boron reagent such as sodium cyanoborohydrideetc. at 0˜50° C.

(9) In the compounds of the formula (Ib), wherein R² is C2-4 alkenylene,i.e. the compounds of the formula (Ib-5)

(wherein R²⁵ is C2-4 alkenylene and the other symbols are ashereinbefore defined.)

may be prepared by reacting the compound of the formula (XI)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (IX)

X—Z⁴—Z^(5b)  (IX)

(wherein all symbols are as hereinbefore defined.)

to form sulfonamide bond or carboamide bond.

Reaction to form sulfonamide bond or carboamide bond may be carried outas the method described in the said (7).

(10) In the compounds of the formula (Ib), wherein R² is C2-4 alkylene,i.e. the compounds of the formula (Ib-6)

(wherein R²⁶ is C2-4 alkylene, Z^(1cc), Z^(5cc) and Z^(4cc) are asZ^(1b), Z^(5b) and Z^(4b), respectively, with the proviso that none ofZ^(1cc), Z^(5cc) and Z^(4cc) are alkenylene, alkynylene,alkenylene-containing group and alkynylene-containing group, and theother symbols are as hereinbefore defined.)

may be prepared by catalytic reduction of the compound of the formula(Ib-5).

The catalytic reduction is known, and for example, this reaction may becarried out under the condition of atmosphere of hydrogen gas, in anorganic solvent (THF, alkanol or acetone etc.), using a reductivecatalyst (Pd, Pd—C, Pt or platinum oxide etc.) at 0˜50° C.

(11) In the compounds of the formula (Ib), wherein R² is C2-4alkynylene, i.e. the compounds of the formula (Ib-7)

(wherein R²⁷ is C2-4 alkynylene, and the other symbols are ashereinbefore defined.)

may be prepared by reacting the compound of the formula (XII)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (IX)

X—Z⁴—Z^(5b)  (IX)

(wherein all symbols are as hereinbefore defined.)

to form sulfonamide bond or carboamide bond.

Reaction to form sulfonamide bond or carboamide bond may be carried outas the method described in the said (7).

(12) In the compounds of the formula (Ib), wherein R² is NZ⁶SO₂ (whereinall symbols are as hereinbefore defined.), i.e. the compounds of theformula (Ib-8)

(wherein R²⁸ is NZ⁶SO₂ (wherein all symbols are as hereinbeforedefined.), and the other symbols are as hereinbefore defined.)

may be prepared by reacting the compound of the formula (Z-1)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (Z-2)

(wherein all symbols are as hereinbefore defined.)

to form sulfonamide bond.

Reaction to form sulfonamide bond may be carried out as the methoddescribed in the said (7).

(13) In the compounds of the formula (Ib), wherein R² is CO, CO-C1-4alkylene, C1-4 alkylene-CO or C1-3 alkylene-CO-C1-3 alkylene, i.e. thecompounds of the formula (Ib-9)

(wherein R²⁹is CO, CO-C1-4 alkylene, C1-4 alkylene-CO or C1-3alkylene-CO-C1-3 alkylene, and the other symbols are as hereinbeforedefined.)

may be prepared by reacting the compound of the formula (Z-3)

(wherein all symbols are as hereinbefore defined.)

with the compound of the formula (Z-4)

(wherein all symbols are as hereinbefore defined.)

This reaction may be carried out, for example, in organic solvent (THF,methylene chloride, benzene, acetone, acetonitrile etc.) in the presenceof Zn or cyano copper at −78° C. to room temperature.

(14) In the compounds of the formula (Ib), wherein R^(4b) is group otherthan H, i.e. the compounds of the formula (Ib-10)

(wherein R⁴⁴ is as R⁴ other than H, and the other symbols are ashereinbefore defined.)

may be prepared by reacting the compound of the formula (Ib-11)

(wherein all symbols are as hereinbefore defined.)

and (a) the compound of the formula (Z-5)

X—R⁴⁴  (Z-5)

(wherein all symbols are as hereinbefore defined.)

or (b) the compound of the formula (Z-6)

HO—R⁴⁴  (Z-6)

(wherein all symbols are as hereinbefore defined.).

The above reaction is N-alkylation reaction or corresponding reaction.For example, this reaction (a) in case of using alkyl halide of theformula

X—R⁴⁴

(wherein all symbols are as hereinbefore defined.),

may be carried out in organic solvent (acetone, THF or methylenechloride etc.), in the presence of base (potassium carbonate etc.) at0˜50° C.

The reaction (b) in case of using alcohol of the formula

HO—R⁴⁴

(wherein all symbols are as hereinbefore defined.),

may be carried out in organic solvent (acetone, THF or methylenechloride etc.), in the presence of triphenylphosphine anddiethyldiazocarboxylate (DEAD) at 0˜50° C.

(15) The compounds wherein R³ is hydroxymethyl may be prepared by themethod mentioned above or the method described in the Exampleshereinafter.

(16) The compounds wherein Z⁴ is SO₂ and Z⁵ is cyclopentyl, cyclohexyl(each ring may be substituted by 1-5 of R⁵ (R⁵ is as hereinbeforedefined.).) or isopropyl may be prepared by the method mentioned aboveor the method described in the Examples hereinafter.

(17) The compounds wherein symbol(s) other than Z¹ is/are COOH, COOZ^(a)(wherein Z^(a) is C1-4 alkyl) or hydroxy or group containing COOH,COOZ^(a) (wherein Z^(a) is as hereinbefore defined.) or hydroxy may beprepared by reacting under the condition that each of the above groupsand Z¹ if necessay are protected by a protecting group which isremovable under an alkaline, acidic or neutral condition and removing aprotecting group under an alkaline, acidic or neutral condition orcombining removal of protecting groups under different conditions (forexample, removal of a protecting group under an acidic condition andremoval of a protecting group under an alkaline condition may be carriedout successively, either reaction being started first.).

A protecting group of COOH which is removable under an acidic conditionincludes, for example, silyl containing group such ast-butyldimethylsilyl etc. or t-butyl.

A protecting group of COOH which is removable under an alkalinecondition includes alkyl group (for example, methyl etc.) other thant-butyl.

A protecting group of COOH which is removable under both an acidiccondition and an alkaline condition includes, for example,methoxymethyl.

A protecting group of COOH which is removable under a neutral conditionincludes benzyl etc.

A protecting group of hydroxy which is removable under an acidiccondition includes, for example, tetrahydoropyranyl, silyl containinggroup such as t-butyidimethylsilyl etc. 1-ethoxyethyl or methoxymethyletc.

A protecting group of hydroxy which is removable under an alkalinecondition includes acyl group such as acetyl etc.

A protecting group of hydroxy which is removable under a neutralcondition includes benzyl or silyl containing group such ast-butyidimethylsilyl etc.

The removal of a protecting group under an alkaline condition is wellknown. For example, this reaction may be carried out in an organicsolvent (methanol, THF, dioxane etc.), using a hydroxide of an alkalimetal (sodium hydroxide, potassium hydroxide etc.), a hydroxide of analkaline earth metal (calcium hydroxide etc.) or a carbonate salt(sodium carbonate, potassium carbonate etc.) or an aqueous solutionthereof, or mixture thereof at 0˜40° C.

The removal of a protecting group under an acidic condition is wellknown. For example, this reaction may be carried out in a solvent(methylene chloride, dioxane, ethyl acetate, acetic acid, water ormixture thereof etc.), using an organic acid (trifluoroacetic acid etc.)or an inorganic acid (HCl, HBr etc.) at 0˜120° C.

The removal of a protecting group under a neutral condition is wellknown. For example, this reaction using benzyl may be carried out in asolvent (ether (THF, dioxane, dimethoxyethane, diethyl ether etc.),alcohol (methanol, ethanol etc.), benzene (benzene, toluene etc.),ketone (acetone, methylethyl ketone etc.), nitrile (acetonitrile etc.)amide (dimethylformamide etc.) water, ethyl acetate, acetic acid ormixture thereof etc.) in the presence of catalyst (Pd—C, palladiumblack, PdOH, PtO₂, Raney nickel etc.), at ordinary or increased pressureunder the condition of atmosphere of hydrogen gas or in the presence ofammonium formate at 0˜200° C.

This reaction using silyl containing group such as t-butyldimethylsilyletc. may be carried out in a solvent such as ether (THF etc.), usingtetrabutylammonium fluoride at 0˜50° C.

The compounds of the formula (III), (V), (VII), (IX), (VII-a), (VII-b),(Z-2), (Z-4), (Z-5) or (Z-6) are known or may be prepared easily byknown methods or the methods described in the Examples hereinafter. Thecompounds of the formula (IV), (VI), (VIII), (X), (XI), (XII) or (Z-3)may be prepared by the following reaction schemes (A)-(F).

In each reaction scheme, each symbol is as hereinbefore defined, or asdefined as follows.

R²⁰⁰: single bond or C1-4 alkylene;

R²⁰²: single bond or C1-4 alkylene;

R²⁰³: single bond or C1-4 alkylene;

R²⁰⁴: single bond or C1 or 2 alkylene;

R²⁰⁵: C1, 2 or 3 alkylene;

R²⁰⁶: single bond or C1 or 2 alkylene;

R²⁰⁷: C1, 2 or 3 alkylene;

R²⁰⁸: C1 or 2 alkylene;

R⁵⁰: C1-4 alkyl;

R⁵¹: trifluoroacetyl;

X¹, X², X³, X⁴: halogen.

In each reaction in the present specification, obtained products may bepurified by conventional techniques. For example, purification may becarried out by distillation at atmospheric or reduced pressure, by highperformance liquid chromatography, by thin layer chromatography or bycolumn chromatography using silica gel or magnesium silicate, by washingor by recrystallization. Purification may be carried out after eachreaction, or after a series of reactions.

Starting Materials and Reagents

The other starting materials and reagents in the present invention areknown per se or may be prepared by known methods.

INDUSTRIAL AVAILABILITY Pharmacological Activity of the PresentInvention Compounds

The compounds of the present invention of the formula (I) can bind tothe receptors of prostaglandin E₂ and show antagonistic activity againstthe action thereof or agonistic activity, so they are useful as PGE₂antagonists or agonists.

As mentioned hereinbefore, to antagonize against PGE₂ is linked toinhibition of uterine contraction, analgesic action, inhibition ofdigestive peristalsis, induction of sleep or increase of vesicalcapacity. Therefore, PGE₂ antagonists are considered to be useful forthe prevention of abortion, as analgesics, as antidiarrheals, as sleepinducers or as agents for treating pollakiuria.

As mentioned hereinbefore, to show PGE₂ agonistic activity is linked touterine contraction, promotion of digestive peristalsis, suppression ofgastric acid secretion or reduction of blood pressure or diuresis.Therefore, PGE₂ agonists are considered to be useful as abortifacient,cathartic, antiulcer, anti-gastritis, antihypertensive or diureticagents.

For example, in standard laboratory test, it was confirmed that thecompounds of the formula (I) of the present invention can bind toreceptor of PGE₂ (EP₁ receptor) according to assay using expression cellof prostanoid receptor subtype.

(i) Bindina Assay Using Expression Cell of Prostanoid Receptor Subtype

The preparation of membrane fraction was carried out according to themethod of Sugimoto et al (J. Biol. Chem. 267, 6463-6466 (1992)), usingexpression CHO cell of prostanoid receptor subtype (mouse EP1).

The standard assay mixture contained membrane fraction (0.5 mg/ml),³H-PGE₂ in a final volume of 200 μl was incubated for 1 hour at roomtemperature. The reaction was terminated by addition of 3 ml of ice-coldbuffer. The mixture was rapidly filtered through a glass filter (GF/B).The radioactivity associated with the filter was measured by liquidscintillation counting.

Kd and Bmax values were determined from Scatchard plots (Ann. N.Y. Acad.Sci., 51, 660 (1949)). Non-specific binding was calculated as the bondin the presence of an excess (2.5 μM) of unlabeled PGE₂. In theexperiment for competition of specific ³H-PGE₂ binding by the compoundsof the present invention, ³H-PGE₂ was added at a concentration of 2.5 nMand the compound of the present invention was added at a variousconcentration of. The following buffer was used in all reaction.

Buffer: potassium phosphate (pH6.0, 10 mM), EDTA (1 mM), MgCl₂ (10 mM),NaCl (0.1M).

The dissociation constant Ki (μM) of each compound was calculated by thefollowing equation.

Ki=IC50/(1+([C]/Kd))

The results were shown in Table 1.

TABLE 1 dissociation constant Example No. Ki (μM) 2 (k) 0.099 18 (30)0.0016 18 (38) 0.016 18 (58) 0.0062 18 (75) 0.0054 18 (94) 0.0004 18(102) 0.0002 20 (20) 0.0099 22 (3) 0.48 24 0.0058 24 (9) 0.018 30 0.07338 0.16 43 0.38 44 0.0013 48 0.01

Toxicity

The toxicity of the compounds of the present invention is very low andtherefore, it is confirmed that these compounds are safe for use asmedicine.

Application for Pharmaceuticals

The compounds of the present invention of the formula (I) can bind tothe receptors of prostaglandin E₂ and show antagonistic activity againstthe action thereof or agonistic activity, so they are useful as PGE₂antagonists or agonists.

As mentioned hereinbefore, to antagonize against PGE₂ is linked toinhibition of uterine contraction, analgesic action, inhibition ofdigestive peristalsis, induction of sleep or increase of vesicalcapacity. Therefore, PGE₂ antagonists are considered to be useful forthe prevention of abortion, as analgesics, as antidiarrheals, as sleepinducers or as agents for treating pollakiuria.

As mentioned hereinbefore, to show PGE₂ agonistic activity is linked touterine contraction, promotion of digestive peristalsis, suppression ofgastric acid secretion or reduction of blood pressure or diuresis.Therefore, PGE₂ agonists are considered to be useful as abortifacient,cathartic, antiulcer, anti-gastritis, antihypertensive or diureticagents.

The compounds of the present invention can bind to receptors ofprostaglandin E₂, especially, EP1 receptor strongly, so they areexpected to be useful as analgesics or as agents for treatingpollakiuria.

For the purpose above described, the compounds of the formula (I),non-toxic salts thereof and hydrates thereof may be normallyadministered systemically or locally, usually by oral or parenteraladministration.

The doses to be administered are determined depending upon age, bodyweight, symptom, the desired therapeutic effect, the route ofadministration, and the duration of the treatment etc. In the humanadult, the doses per person per dose are generally between 1 μg and 100mg, by oral administration, up to several times per day, and between 0.1μg and 10 mg, by parenteral administration (preferred into vein) up toseveral times per day, or continuous administration between 1 and 24hours per day into vein.

As mentioned above, the doses to be used depend upon various conditions.Therefore, there are cases in which doses lower than or greater than theranges specified above may be used.

On administration of the compounds of the present invention, it is usedas solid compositions, liquid compositions or other compositions fororal administration, as injections, liniments or suppositories etc. forparenteral administration.

Solid compositions for oral administration include compressed tablets,pills, capsules, dispersible powders, and granules etc.

Capsules contain hard capsules and soft capsules.

In such solid compositions, one or more of the active compound(s) is orare, admixed with at least one inert diluent such as lactose, mannitol,mannit, glucose, hydroxypropyl cellulose, microcrystalline cellulose,starch, polyvinylpyrrolidone, magnesium metasilicate aluminate. Thecompositions may also comprise, as is normal practice, additionalsubstances other than inert diluents: e.g. lubricating agents such asmagnesium stearate, disintegrating agents such as cellulose calciumglycolate, and assisting agents for dissolving such as glutamic acid orasparaginic acid. The tablets or pills may, if desired, be coated withfilm of gastric or enteric material such as sugar, gelatin,hydroxypropyl cellulose or hydroxypropyl cellulose phthalate etc., or becoated with two or more films. And further, coating may includecontainment within capsules of absorbable materials such as gelatin.

Liquid compositions for oral administration includepharmaceutically-acceptable emulsions, solutions, syrups and elixirsetc. In such liquid compositions, one or more of the active compound(s)is or are comprised in inert diluent(s) commonly used in the art (forexample, purified water, ethanol etc.). Besides inert diluents, suchcompositions may also comprise adjuvants such as wetting agents,suspending agents, sweetening agents, flavouring agents, perfumingagents and preserving agents.

Other compositions for oral administration include spray compositionswhich may be prepared by known methods and which comprise one or more ofthe active compound(s). Spray compositions may comprise additionalsubstances other than inert diluents: e.g. stabilizing agents such assodium hydrogen sulfate, stabilizing agents to give the title compoundisotonicity, isotonic buffer such as sodium chloride, sodium citrate,citric acid. For preparation of such spray compositions, for example,the method described in the U.S. Pat. Nos. 2,868,691 or 3,095,355 may beused.

Injections for parenteral administration include sterile aqueous ornon-aqueous solutions, suspensions and emulsions. Aqueous solutions orsuspensions include distilled water for injection and physiological saltsolution. Non-aqueous solutions or suspensions include propylene glycol,polyethylene glycol, plant oil such as olive oil, alcohol such asethanol, POLYSORBATE80 (registered trade mark) etc. Such compositionsmay comprise additional diluents: e.g. preserving agents, wettingagents, emulsifying agents, dispersing agents, stabilizing agent,assisting agents such as assisting agents for dissolving (for example,glutamic acid, asparaginic acid). They may be sterilized for example, byfiltration through a bacteria-retaining filter, by incorporation ofsterilizing agents in the compositions or by irradiation. They also bemanufactured in the form of sterile solid compositions and which can bedissolved in sterile water or some other sterile diluents for injectionimmediately before used.

Other compositions for parenteral administration include liquids forexternal use, and endemic liniments, ointment, suppositories andpessaries which comprise one or more of the active compound(s) and maybe prepared by known methods.

BEST MODE TO PRACTICE THE INVENTION

The following reference examples and examples are intended toillustrate, but not limit, the present invention.

The solvents in parentheses show the developing or eluting solvents andthe ratios of the solvents used are by volume in chromatographicseparations. Without special explanation, NMR data was determined inCDCl₃ solution.

REFERENCE EXAMPLE 1 5-Chloroanthranilic Acid Methyl Ester

To a suspension of 5-chloroanthranilic acid (6.1 g) in AcOEt-MeOH (20ml+10 ml), a solution of an excess amount of diazomethane in ether (50ml) was added at 0° C. After termination of reaction, reaction solventwas evaporated to dryness to give the title compound (6.6 g) having thefollowing physical data.

NMR: δ 7.82 (1H, d), 7.21 (1H, dd), 6.60 (1H, d), 5.73 (2H, brs), 3.88(3H, s).

REFERENCE EXAMPLE 2 Methyl 2-Phenylsulfonylamino-5-chlorobenzoate

To a solution of 5-chloroanthranilic acid methyl ester (400 mg;.prepared in Reference Example 1.) and pyridine (0.87 ml) in methylenechloride, benzenesulfonylchloride (0.33 ml) was added at 0° C. Thesolution was stirred overnight at room temperature. The reaction mixturewas poured into diluted HCl and extracted with ethyl acetate. Theorganic layer was washed, dried over and concentrated under reducedpressure. The residue was purified on silica gel column chromatography(hexane-AcOEt) to give the title compound (664 mg) having the followingphysical data.

TLC: Rf 0.30 (hexane:AcOEt=4:1); NMR: δ 10.5 (1H, s), 7.90-7.79 (3H, m),7.79 (1H, d), 7.60-7.37 (4H, m), 3.88 (3H, s).

REFERENCE EXAMPLE 3 2-Phenylsulfonylamino-5-chlorobenzoic Acid

To a solution of methyl 2-phenylsulfonylamino-5-chlorobenzoate (600 mg;prepared in Reference Example 2.) in the mixture of THF-MeOH (6 ml+3ml), 2N NaOH solution (2 ml) was added. The mixture was stirred for 2days. To the reaction mixture, 1N HCl (4.5 ml) was added. The mixturewas extracted with ethyl acetate. The organic layer was washed and driedover to give the title compound (575 mg) having the following physicaldata.

NMR: δ 10.31 (1H, s), 7.99 (1H, d), 7.92-7.83 (2H, m), 7.70 (1H, d),7.63-7.42 (4H, m), 6.20 (1H, brs).

EXAMPLE 1 Methyl 4-(2-Phenylsulfonylamino-5-chlorobenzoylamino)benzoate

To a suspension of 2-phenylsulfonylamino-5-chlorobenzoic acid (250 mg;prepared in Reference Example 3.) and methyl p-aminobenzoate (133 mg) inmethylene chloride (5 ml), EDC (168 mg) and dimethylaminopyridine (20mg) were added. The mixture was stirred for 3 days at room temperature.The reaction mixture was poured into diluted HCl and extracted withethyl acetate. The organic layer was washed, dried over and concentratedunder reduced pressure. The residue was purified on silica gel columnchromatography (AcOEt-benzene) to give the title compound (142 mg)having the following physical data.

TLC: Rf 0.29 (AcOEt:benzene=1:9); NMR (CDCl₃+DMSO-d₆): δ 10.40 (1H, s),9.90 (1H, m), 8.03 (2H, d), 7.82-7.70 (5H, m), 7.63 (1H, d), 7.50-7.24(4H, m), 3.93 (3H, s).

EXAMPLE 2 4-(2-Phenylsulfonylamino-5-chlorobenzoylamino)benzoic Acid

To a solution of methyl4-(2-phenylsulfonylamino-5-chlorobenzoyl-amino)benzoate (122 mg;prepared in Example 1.) in THF-MeOH (4 ml+2 ml), 2N NaOH aqueoussolution (0.5 ml) was added at room temperature. The mixture was stirredovernight. To the reaction mixture, 2N HCl (0.6 ml) and water wereadded. The mixture was extracted with ethyl acetate. The organic layerwas washed, dried over and concentrated under reduced pressure. Theresidue was purified by recrystallization from the mixture ofAcOEt-hexane to give the title compound (80 mg) having the followingphysical data.

TLC: Rf 0.32 (MeOH: CH₂Cl₂=15:85); NMR (DMSO-d₆): δ 12.74 (1H, brs),10.61 (1H, s), 10.40 (1H, s), 7.95 (2H, d), 7.85-7.71 (5H, m), 7.64-7.35(5H, m).

EXAMPLE 2(a)-2(bb)

The title compounds having the following physical data were obtained bythe same procedure of Reference Example 1 Reference Example 3 andExamples 1 and 2.

EXAMPLE 2(a) 3-(2-Phenylsulfonylaminobenzoylamino)benzoic Acid

TLC: Rf 0.57 (CHCl₃:MeOH:AcOH=100:10:1); NMR (DMSO-d₆): δ 13.01 (1H,brs), 10.66 (1H, brs), 10.50 (1H, brs), 8.32 (1H, brs), 7.89 (1H, d),7.76 (4H, m), 7.51 (6H, m), 7.23 (1H, m).

EXAMPLE 2(b) 3-(2-Phenylsulfonylamino-5-chlorobenzoylamino)benzoic Acid

TLC: Rf 0.26 (MEOH:CHCl₃=15:85); NMR (CDCl₃:DMSO-d₆=1:1): δ 12.70 (1H,brs), 10.69 (1H, s), 10.44 (1H, s), 8.27 (1H, t), 7.95-7.69 (5H, m),7.59-7.36 (6H, m).

EXAMPLE 2(c) 4-(2-Phenylsulfonylaminobenzoylamino)benzoic Acid

TLC: Rf 0.50 (CHCl₃:MeOH:AcOH=100:10:1); NMR (DMSO-d₆): δ 12.76 (1H,brs), 10.57 (1H, s), 10.49 (1H, s), 7.95 (2H, d), 7.77 (5H, m),7.28-7.62 (5H, m), 7.24 (1H, m).

EXAMPLE 2(d)4-[2-(4-Chlorophenyl)sulfonylamino-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.27 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 12.70 (1H, br s),10.59 (1H, s), 10.30 (1H, s), 7.95 (2H, d), 7.83-7.66 (5H, m), 7.62-7.47(3H, m), 7.34 (1H, d).

EXAMPLE 2(e)4-[2-(4-ChlorophenyIsulfonylamino)-4-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.69 (CHCl₃:MeOH:AcOH=17:2:1); NMR (CDCl₃+DMSO-d₆): δ 10.9-10.3(1H, br), 10.3-9.9 (1H, br), 7.84 (2H, d), 7.7-7.5 (5H, m), 7.45 (1H,s-like), 7.17 (2H, d), 7.0-6.9 (1H, m).

EXAMPLE 2(f)4-[2-(4-Chlorophenylsulfonylamino)-6-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.67 (CHCl₃:MeOH:AcOH=17:2:1); NMR: δ 9.64 (1H, s-like), 7.8-7.7(2H, m), 7.5-7.3 (4H, m), 7.1-6.9 (5H, m).

EXAMPLE 2(g)4-[2-(4-Chlorophenylsulfonylamino)-3-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.32 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.8-12.6 (1H, br),10.7-10.5 (1H, br), 10.12 (1H, s), 7.89 (2H, d), 7.7-7.5 (6H, m),7.5-7.3 (3H, m).

EXAMPLE 2(h)4-[2-(2-Chlorophenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.16 (CHCl₃:MeOH=M9:1); NMR (DMSO-d₆): δ 12.78 (1 H, br), 10.80(2H, br), 8.08-8.03 (1H, m),7.95 (2H, d), 7.88 (1H, d), 7.80 (2H, d),7.66-7.46 (4H, m), 7.38 (1H, d).

EXAMPLE 2(i)4-[2-(3-Chlorophenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.15 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.76 (1H, br), 10.62(1H, brs), 10.36 (1H, brs), 7.92 (2H, d), 7.77-7.73 (4H, m), 7.67-7.44(4H, m), 7.28 (1H, d).

EXAMPLE 2(j) 4-[2-(4-Chlorophenylsulfonylarnino)-5-fluorobenzoylaminobenzoic Acid

TLC: Rf 0.28 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 12.78 (1H, brs), 10.50(1H, s), 10.09 (1H, s), 7.95 (2H, d), 7.75 (2H, d), 7.68-7.26 (7H, m).

EXAMPLE 2(k)4-[2-(4-Chlorophenylsulfonylamino)-5-bromobenzoylamino]benzoic Acid

TLC: Rf 0.28 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 12.74 (1H, brs), 10.61(1H, s), 10.33 (1H, s), 7.95 (2H, d), 7.89 (1H, d), 7.81-7.65 (5H, m),7.53 (2H, d), 7.29 (1H, d).

EXAMPLE 2(l)4-[2-(4-Chlorophenylsulfonylamino)-5-methoxybenzoylamino]benzoic Acid

TLC: Rf 0.30 (MeOH CHCl₃=15:85); NMR (DMSO-d₆): δ 12.77 (1H, brs), 10.39(1H, s), 9.79 (1H, s), 7.94 (2H, d), 7.73 (2H, d), 7.59 (2H, d), 7.43(2H, d), 7.25-7.15 (2H, m), 7.09 (1H, dd).

EXAMPLE 2(m)4-[2-(4-Bromophenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.27 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.74 (1H, br), 10.55(1H, brs), 10.27 (1H, brs), 7.92 (2H, d), 7.75-7.71 (3H, m), 7.66-7.51(5H, m), 7.31 (1H, d).

EXAMPLE 2(n)4-[2-(4-Methylphenylsulfonylamino)-5-chlornbenzoylamino]benzoic Acid

TLC: Rf 0.30 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.76 (1H, br), 10.56(1H, brs), 10.23 (1H, brs), 7.93 (2H, d), 7.77-7.73 (3H, m), 7.60-7.51(3H, m), 7.36 (1H, d),7.23 (2H, d),2.24 (3H, s).

EXAMPLE 2(o)4-[2-(4-Methoxyphenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.29 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.76 (1H, br), 10.57(1H, brs), 10.16 (1H, brs), 7.93 (2H, d), 7.77-7.73 (3H, m), 7.62 (2H,d), 7.59-7.52 (1H, m), 7.37 (1H, d), 6.93 (2H, d), 3.70 (3H, s).

EXAMPLE 2(p)4-[2-(4-Nitrophenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.10 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.71 (1H, br),10.55-10.35 (2H, br), 8.19 (2H, d), 7.93-7.86 (4H, m), 7.71-7.64 (3H,m), 7.58-7.52 (1H, m), 7.32 (1H, d).

EXAMPLE 2(q)4-[2-(2,4-Dichlorophenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.22 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.50 (1H, br), 10.73(2H, br), 7.99-7.91 (3H, m), 7.85 (1H, d-like), 7.79-7.71 (3H, m),7.58-7.51 (2H, m), 7.36 (1H, d).

EXAMPLE 2(r)4-2-(4-Butylphenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.33 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.72 (1H, br), 10.55(1H, brs), 10.24 (1H, s), 7.92 (2H, d), 7.78-7.72 (3H, m), 7.60 (2H, d),7.57-7.51 (1H, m), 7.37 (1H, d), 7.24 (2H, d), 2.54-2.49 (2H, m),1.48-1.33 (2H, m), 1.29-1.11 (2H, m), 0.82 (3H, t).

EXAMPLE 2(s) 4-[2-(4-Chlorophenylsulfonylamino)benzoylamino]benzoic Acid

TLC: Rf 0.30 (AcOEt:hexane:AcOH=7:16:1); NMR (DMSO-d₆): δ 13.00-12.60(1H, brs), 10.55 (1H, brs), 10.38 (1H, brs), 7.95 (2H, d), 7.78 (2H, d),7.74 (1H, m), 7.72 (2H, d), 7.51 (2H, d), 7.50 (1H, m), 7.40-7.24 (2H,m).

EXAMPLE 2(t) 4-(2-Phenylsulfonylamino-5-fluorobenzoylamino)benzoic Acid

TLC: Rf 0.23 (CHCl₃:MEOH=9:1); NMR (DMSO-d₆): δ 12.70 (1H, br), 10.52(1H, br), 10.13 (1H, br), 7.92 (2H, d), 7.74 (2H, d), 7.68-7.64 (2H, m),7.59-7.27 (6H, m).

EXAMPLE 2(u) 4-(2-Phenylsulfonylamino-4-fluorobenzoylamino)benzoic Acid

TLC: Rf 0.20 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.81 (1H, br), 10.85(1H, br), 10.60 (1H, br), 7.95-7.74 (7H, m), 7.63-7.46 (3H, m),7.19-7.02 (2H, m).

EXAMPLE 2(v)4-[2-(4-Chlorophenylsulfonylamino)-4-fluorobenzoylamino]benzoic Acid

TLC: Rf 0.22 (CHCl₃:MEOH=9:1), NMR (DMSO-d₆): δ (12.28 (1H, br), 10.75(1H, br), 10.58 (1H, br), 7.95-7.72 (7H, m), 7.53 (2H, d), 7.19-7.08(2H, m).

EXAMPLE 2(w)4-[2-(4-Fluorophenylsulfonylamino)-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.26 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.75 (1H, br), 10.58(1H, br), 10.27 (1H, brs), 7.93 (2H, d), 7.80-7.72 (5H, m), 7.54 (1H,dd), 7.34-7.22 (3H, m).

EXAMPLE 2(x)4-[2-(4-Trifluoromethylphenylsulfonyaminio)-5-chlorobenzoylamino]benzoicAcid

TLC: Rf 0.26 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.70 (1H, br), 10.56(1H, br), 10.41 (1H, br), 7.92-7.68 (9H, m), 7.54 (1H, dd-like), 7.31(1H, d).

EXAMPLE 2(y) 4-(2-Phenylsulfonylamino-5-chlorobenzoylaminomethyl)benzoicAcid

TLC: Rf 0.45 (MeOH:CHCl₃=1:4); NMR (DMSO-d₆): δ 12.90 (1H, s), 11.47(1H, s), 9.46 (1H, t), 7.94 (2H, d), 7.86 (1H, d), 7.77-7.36 (9H, m),4.48 (1H, d).

EXAMPLE 2(z)4-[2-(2-Phenylvinyl)sulfonylamino-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.43 (CHCl₃:MeOH=9:1); NMR (CD3OD): δ 7.98 (2H, d), 7.83 (1H,d), 7.72 (2H, d), 7.63 (1H, d), 7.53 (1H, dd), 7.5-7.2 (6H, m), 7.01(1H, d).

EXAMPLE 2(aa)4-[2-(2-Phenylethyl)suffonylamino-5-chlorobenzoylamino]benzoic Acid

TLC: Rf 0.27(CHCl₃:MeOH 9:1); NMR (DMSO-d₆): δ 12.75 (1H, br), 10.78(1H, brs), 10.05 (1H, s), 7.95-7.79 (5H, m), 7.63-7.53 (2H, m),7.24-7.10 (5H, m), 3.53-3.45 (2H, m), 2.99-2.91 (2H, m).

EXAMPLE 2(bb)4-[2-(4-Chlorophenylsulfonylamino)-5-nitrobenzoylamino]benzoic Acid

TLC: Rf 0.32 (AcOEt:hexane:AcOH=4:12:1); NMR (DMSO-d₆): δ 12.50-10.00(2H, brs), 8.66 (1H, d), 8.36-8.24 (1H, dd), 8.05-7.87 (4H, m), 7.80(2H, d), 7.68-7.55 (3H, m).

EXAMPLE 34-[2-(4-Hydroxyphenyisulfonylamino)-5-chlorobenzoylamino]benzoic Acid

To a mixture solution of methyl4-[2-(4-pivaroyloxyphenylsulfonylamino)-5-chlorobenzoylamino]benzoate(214 mg; prepared by the same procedure as Reference Examples 1, 2 and 3and Example 1. ) in MeOH-THF (8 ml+3 ml), 2N NaOH aqueous solution (2ml) was added. The mixture was stirred for one day at 60° C. To thereaction solution, HCl was added. The mixture was extracted with ethylacetate. The organic layer was washed, dried over and purified byrecrystallization from the mixture solvent of MeOH-AcOEt-hexane to givethe title compound (105 mg) having the following physical data.

TLC: Rf 0.42 (CHCl₃:MeOH:AcOH=45:4:1); NMR (DMSO-d₆): δ 13.0-12.6 (1H,br), 10.64 (1H, s-like), 10.50 (1H, s-like), 10.21 (1H, s), 7.95 (2H,d), 7.9-7.7 (3H, m), 7.6-7.3 (4H, m), 6.76 (2H, d).

REFERENCE EXAMPLE 4 Methyl4-[2-(2-Nitro-5-chlorophenyl)-(EZ)-vinyl]benzoate

To a solution of 4-methoxycarbonylphenylmethyltriphenylphosphine bromide(4.83 g) in THF (20 ml), potassium t-butoxide (600 mg) was added. Themixture was stirred for 1 hour at room temperature. To the reactionsolution, 2-nitro-5-chlorobenzaldehyde (742 mg) was added at 0° C. Themixture was stirred for 30 minutes at room temperature. The reactionmixture was poured into diluted HCl. The mixture was extracted withhexane-AcOEt. The organic layer was washed, dried over and concentratedunder the reduced pressure. The residue was purified on silica gelcolumn chromatography (hexane-AcOEt) and recrystallization from themixture solvent of hexane-AcOEt to give the title compound (680 mg)having the following physical data.

TLC: Rf 0.44 (hexane:AcOEt=4:1).

REFERENCE EXAMPLE 5 Methyl4-[2-(2-Amino-5-chlorophenyl)-(E)-vinyl]benzoate and Methyl4-[2-(2-Amino-5-chlorophenyl)-(Z)-vinyl]benzoate

To a solution of methyl4-[2-(2-nitro-5-chlorophenyl)-(EZ)-vinyl]benzoate (525 mg; prepared inReference Example 4.) in THF (4 ml), water (1.5 ml), 2N HCl and reducediron (554 mg) were added. The mixture was stirred overnight at roomtemperature. Further, to the mixture, 2N HCl (0.2 ml) and reduced ironpowder (330 mg) were added. The mixture was stirred for 3 days. Thereaction mixture was diluted with ethyl acetate and filtrated. Thefiltrate was washed, dried over and concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(ether-hexane-AcOEt) to give the title compound having the followingphysical data.

(E) type compound

TLC: Rf 0.37 (AcOEt:benzene=5:95).

(Z) type compound

TLC: Rf 0.41 (AcOEt:benzene=5:95).

EXAMPLE 4 Methyl4-[2-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenyl]-(E)-vinyl]-benzoate

To methyl 4-[2-(2-amino-5-chlorophenyl)-(E)-vinyl]benzoate (130 mg;prepared in Reference Example 5.) in methylene chloride (3 ml), pyridine(0.073 μl) and p-chlorobenzenesulfonylchloride (114 mg) were added. Themixture was stirred overnight at room temperature. The reaction mixturewas poured into diluted HCl and extracted with ethyl acetate. Theorganic layer was washed, dried over and concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(AcOEt-hexane) to give the title compound (205 mg) having the followingphysical data.

TLC: Rf 0.15 (AcOEt:benzene=4:96); NMR: δ 8.02 (2H, d), 7.63 (2H, d),7.51 (1H, s), 7.41-7.30 (4H, m), 7.26-7.22 (2H, m), 6.91 (1H, d), 6.81(1H, d), 6.63 (1H, s), 3.95 (3H, s).

EXAMPLE 4(a) Methyl4-[2-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenyl]-(Z)-vinyl]-benzoate

By using Z type compound prepared in Reference Example 5, the titlecompound having the following physical data was obtained by the sameprocedure as Example 4.

TLC: Rf 0.23 (AcOEt:benzene=4:96); NMR: δ 7.82 (2H, d), 7.57 (2H, d),7.46 (1H, d), 7.33 (2H, d), 7.24 (1H, dd), 7.06 (1H, d), 6.99 (2H, d),6.72 (1H, d), 6.48 (1H, s), 6.20 (1H, d), 3.90 (3H, s).

EXAMPLE 54-[2-[2-(4-Cholorophenylsulfonylamino)-5-chlorophenyl]-(E)-vinyl]benzoicAcid

By using methyl4-[2-[2-(4-chlorophenylsulfonylamino)-5-chlorophenyl]-(E)-vinyl]benzoate(190 mg; prepared in Example 4.), the title compound (168 mg) having thefollowing physical data was obtained by the same procedure as Example 2.

TLC: Rf 0.36 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 10.11 (1H, brs), 7.96(2H, d), 7.80 (1H, d), 7.59 (2H, d), 7.52-7.41 (4H, m), 7.36 (1H, dd),7.20 (1H, d), 7.15 (1H, d), 7.08 (1H, d).

EXAMPLE 5(a)4-[2-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenyl]-(Z)-vinyl]benzoicAcid

By using methyl4-[2-[2-(4-chlorophenylsulfonylamino)-5-chlorophenyl]-(Z)-vinyl]benzoateprepared in Example 4(a), the title compound having the followingphysical data was obtained by the same procedure as Example 2.

TLC: Rf 0.46 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 10.05 (1H, brs),7.79-7.67 (4H, m), 7.55 (2H, d),7.30 (1H, dd), 7.15 (1H, d), 7.00 (1H,d), 6.91 (1H, d), 6.64 (2H, s).

EXAMPLE 64-[2-[2-(4-Chlorophenyl)sulfonylamino-5-chlorophenyl]ethyl]benzoic Acid

To a solution of4-[2-[2-(4-chlorophenyl)sulfonylamino-5-chlorophenyl]vinyl]benzoic acid(54 mg; prepared in Example 5.) in THF (4 ml), platinum oxide hydrate (3mg) was added. The mixture was stirred for 2 hours at room temperaturein a stream of hydrogen. The reaction mixture was filtered and thefiltrate was concentrated under the reduced pressure. To the residue,methylene chloride was added. The mixture was stirred. The precipitatewas collected by filter to give the title compound (46 mg) having thefollowing physical data.

TLC: Rf 0.42 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 12.75 (H, s), 9.88(1H, s), 7.84 (2H, d), 7.72-7.57 (4H, m), 7.32 (1H, d), 7.23 (2H, d),7.18 (1H, dd), 6.88 (1H, d).

REFERENCE EXAMPLE 6 Methyl4-(2-Trifluoroacetylamino-5-chlorophenoxymethyl)benzoate

To a solution of 2-trifluoroacetylamino-5-chlorophenol (350 mg) andmethyl 4-bromomethylbenzoate (435 mg) in DMF (3 ml), potassium carbonate(263 mg) was added at room temperature. The mixture was stirred for 1.5hours at 60° C. After the termination of reaction, the reaction mixturewas poured into diluted HCl and extracted with ethyl acetate. Theorganic layer was washed, dried over and concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(AcOEt-benzene) to give the title compound (353 mg) having the followingphysical data.

TLC: Rf 0.44 (AcOEt:benzene=5:95).

REFERENCE EXAMPLE 7 Methyl 4-(2-Amino-5-chlorophenoxymethyl)benzoate

To a solution of methyl4-(2-trifluoroacetylamino-5-chlorophenoxymethyl)benzoate (300 mg;prepared in Reference Example 6.) in mixture of THF-MeOH (4 ml+10 ml), asolution of sodium carbonate (440 mg) in water (2 ml) was added. Thesolution was stirred for 8 hours at 60° C. and overnight at roomtemperature. The reaction mixture was poured into diluted HCl andextracted with ethyl acetate. The organic layer was washed, dried overand concentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (AcOEt-benzene) to give the titlecompound (194 mg) having the following physical data.

TLC: Rf 0.27 (AcOEt:benzene=5:95).

EXAMPLE 7 Methyl4-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenoxymethyl]benzoate

By using methyl 4-(2-amino-5-chlorophenoxymethyl)benzoate (165 mg;prepared in Reference Example 7.), the title compound (259 mg) havingthe following physical data was obtained by the same procedure asExample 4.

TLC: Rf 0.30 (AcOEt:benzene=5:95); NMR: δ 8.06 (2H, d), 7.59 (2H, d),7.53 (1H, d), 7.34 (2H, d), 7.18 (2H, d), 6.96 (1H, dd), 6.82 (1H, brs),6.76 (1H, d), 4.89 (2H, s), 3.96 (3H, s).

EXAMPLE 7(a) Methyl4-(2-Phenylsulfonylamino-4-chlorophenoxymethyl)benzoate

By using 2-trifluoroacetylamino-4-chlorophenol, the title compoundhaving the following physical data was obtained by the same procedure asReference Example 6→Reference Example 7→Example 4→Example 2.

TLC: Rf 0.37 (hexane:AcOEt=2:1); NMR: δ 8.01 (2H, d, J=8.4 Hz), 7.75(2H, m), 7.63 (1H, d, J=2.4 Hz), 7.56 (1H, m), 7.43 (2H, m), 7.15 (2H,d, J=8.4 Hz), 6.69 (1H, brs), 6.97 (1H, dd, J=2.4, 8.8 Hz), 6.63 (1H, d,J=8.8 Hz), 4.92 (2H, s), 3.94 (3H, s).

EXAMPLE 84-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenoxymethyl]benzoic Acid

By using methyl4-[2-(4-chlorophenylsulfonylamino)-5-chlorophenoxymethyl]benzoate (210mg; prepared in Example 7.), the title compound (197 mg) having thefollowing physical data was obtained by the same procedure as Example 2.

TLC: Rf 0.43 (MeOH:CHCl₃=15:85); NMR (DMSO-d₆): δ 9.89 (1H, br s), 7.93(2H, d), 7.60 (2H, d), 7.42 (2H, d), 7.34 (2H, d), 7.29 (1H, d), 7.06(1H, d), 7.01 (1H, dd), 4.98 (2H, s).

EXAMPLE 8(a)-8(c)

The title compounds having the following physical data were obtained bythe same procedure as Reference Examples 6, 7 and Examples 7 and 8.

EXAMPLE 8(a) 4-(2-Phenylsulfonylamino-5-chlorophenoxymethyl)benzoic Acid

TLC: Rf 0.39 (MeOH CHCl₃=2:8); NMR (DMSO-d₆): δ 12.98 (1H, s), 9.78 (1H,s), 7.92 (2H, d), 7.65 (2H, d), 7.55 (1H, t), 7.41 (2H, t), 7.37 (2H,d), 7.28 (1H, d), 7.04 (1H, dz), 6.98 (1H, dd), 4.98 (2H, s).

EXAMPLE 8(b) (2-Phenylsulfonylamino-4-chlorophenoxymethyl)benzoic Acid

TLC: Rf 0.40 (MeOH:CHCl₃=2:8); NMR (DMSO-d₆): δ 12.98 (1H, brs), 9.94(1H, s), 7.90 (2H, d), 7.70 (2H, d), 7.58 (1H, t), 7.44 (2H,), 7.36 (2H,d), 7.28 (1H, d), 7.15 (1H, dd), 6.94 (1H, d), 4.97 (2H, s).

EXAMPLE 8(c)4-[2-(4-Chlorophenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.40 (MeOH:CHCl₃=2:8); NMR (DMSO-d₆): δ 12.93 (1H, s), 10.02(1H, s), 7.88 (2H, d), 7.61 (2H, d), 7.42 (2H, d), 7.35-7.22 (3H, m),7.17 (1H, dd), 6.93 (1H, d), 4.94 (2H, s).

REFERENCE EXAMPLE 8 O-mesyl-2-nitro-5-chlorobenzyl Alcohol

A solution of 2-nitro-5-chlorobenzyl alcohol (400 mg) in methylenechloride (6 ml) was cooled by salt-ice. To this solution,triethylamine(0.6 ml) and mesylchloride (0.25 ml) were added. Themixture was stirred for 15 minutes. To the reaction mixture, water wasadded. The mixture was extracted with ethyl acetate. The organic layerwas washed, dried over and concentrated under the reduced pressure togive the title compound (600 mg) having the following physical data.

TLC: Rf 0.36 (hexane:AcOEt=2:1).

REFERENCE EXAMPLE 9 Methyl 4-(2-Nitro-5-chlorophenylmethoxy)benzoate

To a solution of O-mesyl-2-nitro-5-chlorobenzyl alcohol (600 mg;prepared in Reference Example 8.) in acetone (10 ml), methyl4-hydroxybenzoate (425 mg) and potassium carbonate (900 mg) were added.The mixture was stirred for 1 hour. To the reaction mixture, acetone (10ml) was added. The mixture was stirred for 22 hours and filtered. Thefiltrate was concentrated under the reduced pressure. The residue waspurified on silica gel column chromatography (hexane-AcOEt) to give thetitle compound (463 mg) having the following physical data.

TLC: Rf 0.26 (hexane:AcOEt=2:1).

REFERENCE EXAMPLE 10 Methyl 4-(2-Amino-5-chlorophenylmethoxy)benzoate

A mixture of methyl 4-(2-nitro-5-chlorophenylmethoxy)benzoate (460 mg;prepared in Reference Example 9.), THF (10 ml), water (3 ml), 1 N HCl(0.4 ml) and iron powder (500 mg) was stirred for 13 hours. The reactionmixture was filtered. The filtrate was washed, dried over andconcentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (hexane-AcOEt) to give the titlecompound (419 mg) having the following physical data.

TLC: Rf 0.23 (hexane:AcOEt=4:1).

EXAMPLE 9 Methyl4-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenylmethoxy]benzoate

To a solution of methyl 4-(2-amino-5-chlorophenylmethoxy)benzoate (450mg; prepared in Reference Example 10.) in methylene chloride (4 ml),pyridine (0.24 ml) and 4-chlorobenzenesulfonylchloride (380 mg) wereadded. The mixture was stirred for 21 hour. To the reaction mixture,water was added. The mixture was extracted with ethyl acetate. Theorganic layer was washed, dried over and concentrated under the reducedpressure. The residue was purified by recrystallization fromhexane-AcOEt mixture solvent to give the title compound (310 mg) havingthe following physical data.

TLC: Rf 0.45 (benzene:AcOEt=9:1); NMR: δ 8.01 (2H, d), 7.62 (2H, d),7.40 (2H, d), 7.32-7.26 (3H, m), 7.11 (1H, brs), 6.90 (2H, d), 4.80 (2H,s), 3.90 (3H, s).

EXAMPLE 104-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenylmethoxy]benzoic Acid

By using methyl4-[2-(4-chlorophenylsulfonylamino)-5-chlorophenylmethoxy]benzoate (300mg; prepared in Example 9.), the title compound (187 mg) having thefollowing physical data was obtained by the same procedure as Example 2.

TLC: Rf 0.51 (AcOEt); NMR (DMSO-d₆): δ 10.2-10.0 (1H, br), 7.90 (2H, d),7.69 (2H, d), 7.61 (2H, d), 7.49 (1H, d), 7.36 (1H, dd), 7.01 (1H, d),6.92 (2H, d), 5.02 (2H, s).

REFERENCE EXAMPLE 11 2-Phenylsulfonylamino-5-chloro-1-nitrobenzene

To a solution of 2-nitro-4-chloroaniline (500 mg) and pyridine (2.1 mlin methylene chloride (10 ml), benzenesulfonylchloride (1.2 ml) wasadded dropwise at 0° C. under an atmosphere of argon. The reactionmixture was stirred for 3 days at room temperature. To the reactionmixture, water was added. The mixture was extracted with ethyl acetate.The organic layer was washed, dried over and concentrated under thereduced pressure. The reside was recrystallized from AcOEt-hexanemixture solvent to give the by-product. The mother liquor wasconcentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (AcOEt-hexane) and recrystallized fromAcOEt-hexane mixture solvent to give the title compound (175 mg) havingthe following physical data.

TLC: Rf 0.37 (AcOEt:hexane=1:5).

REFERENCE EXAMPLE 12 2-Phenylsulfonylamino-5-chloroaniline

To a solution of 2-phenylsulfonylamino-5-chloro-1-nitrobenzene (172 mg;prepared in Reference Example 11.) in acetic acid (4 ml), reduced ironpowder (154 mg) was added at room temperature under an atmosphere ofargon. The suspension was stirred for 2 hours at 120° C. The reactionsuspension was diluted with ethyl acetate and filtered. The filtrate wasconcentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (AcOEt-hexane) to give the titlecompound (92 mg) having the following physical data.

TLC: Rf 0.34 (AcOEt:hexane=1:2).

EXAMPLE 11 Methyl4-(2-Phenylsulfonylamino-5-chlorophenylaminocarbonyl)benzoate

To a solution of 2-phenylsulfonylamino-5-chloroaniline (90 mg; preparedin Reference Example 12.) and pyridine (0.05 ml) in methylene chloride(5 ml), 4-methoxycarbonylbenzoic acid chloride (70 mg) was added at roomtemperature in a stream of argon. The mixture was stirred for 6 hours.After the termination of reaction, water was added to the reactionmixture. The mixture was extracted with ethyl acetate. The organic layerwas washed, dried over and concentrated under the reduced pressure. Theresidue was purified by the recrystallization from AcOEt-hexane mixturesolvent to give the title compound (112 mg) having the followingphysical data.

TLC: Rf 0.55 (AcOEt hexane=1:1); NMR (CDCl₃+DMSO-d₆): δ 9.41 (1H, brs),8.93 (1H, brs), 8.22 (1H, d), 8.15 (2H, d), 7.98 (2H, d), 7.72-7.62 (2H,m), 7.58-7.45 (1H, m), 7.44-7.32 (2H, m), 6.96 (1H, dd), 6.82 (1H, d).

EXAMPLE 12 4-(2-Phenylsulfonylamino-5-chlorophenylaminocarbonyl)benzoicAcid

By using methyl4-(2-phenylsulfonylamino-5-chlorophenylaminocarbonyl)benzoate (110 mg;prepared in Example 11.), the title compound (107 mg) having thefollowing physical data was obtained by the same procedure as Example 2.

TLC: Rf 0.36 (AcOEt:hexane:ACOH=8:10:1); NMR (DMSO-d₆): δ 13.00 (1H,brs), 9.80 (1H, brs), 9.65 (1H, s), 8.09 (2H, d), 7.87 (2H, d), 7.81(1H, d), 7.65-7.50 (3H, m), 7.40 (2H, t), 7.22 (1H, dd), 7.14 (1H, d).

REFERENCE EXAMPLE 13 2-Nitro-5-chlorobenzoic Acid Chloride

A solution of 2-nitro-5-chlorobenzoic acid (200 mg) in sulfonylchloride(20 ml) was stirred for 4 hours at 99° C. in a stream of argon. Afterleaving to cool, the solution was concentrated under the reducedpressure to give the title compound.

REFERENCE EXAMPLE 141-(2-Nitro-5-chlorobenzoyl)-1-(4-methoxycarbonylphenyl)methylideneTriphenylphosphoran

To a solution of 4-methoxycarbonylbenzyltriphenylphosphonium bromide(1.17 g) in THF (8 ml), potassium t-butoxide (246 mg) was added in astream of argon. The mixture was stirred for 30 minutes. A solution of2-nitro-5-chlorobenzoic acid chloride (prepared in Reference Example13.) in THF (4 ml) was added dropwise to the reaction solution. Themixture was stirred for 3 hours at room temperature. The reactionmixture was quenched by adding saturated aqueous ammonium chloride andextracted with chloroform. The organic layer was washed, dried over andconcentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (CHCl₃—MeOH) to give the title compound(619 mg) having the following physical data.

TLC: Rf 0.26 (CHCl₃:MeOH=100:1).

REFERENCE EXAMPLE 15 Methyl4-[2-(2-Nitro-5-chlorophenyl)ethynyl]benzoate

A solution of1-(2-nitro-5-chlorobenzoyl)-1-(4-methoxycarbonylphenyl)methylidenetriphenylphosphoran (513 mg; prepared in Reference Example 14.) ino-dichlorobenzene (10 ml) was refluxed for 9 hours at 180° C. in astream of argon. The reaction mixture was concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(hexane-AcOEt) to give the title compound (189 mg) having the followingphysical data.

TLC: Rf 0.39 (hexane:AcOEt=7:1).

REFERENCE EXAMPLE 16 Methyl4-[2-(2-Amino-5-chlorophenyl)ethynyl]benzoate

To a solution of methyl 4-[2-(2-nitro-5-chlorophenyl)ethynyl]benzoate(180 mg; prepared in Reference Example 15.) in acetic acid (3.6 ml),reduced iron powder (160 mg) was added. The mixture was refluxed for 30minutes and filtered. The filtrate was concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(hexane-AcOEt) to give the title compound (144 mg) having the followingphysical data.

TLC: Rf 0.25 (hexane:AcOEt=5:1).

EXAMPLE 13 Methyl4-[2-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenyl]ethynyl]benzoate

To a solution of methyl 4-[2-(2-amino-5-chlorophenyl)ethynyl]benzoate(136 mg; prepared in Reference Example 16.) in methylene chloride (2ml), pyridine (77 μl) and 4-chlorobenzenesulfonyl chloride (106 mg) wereadded at 0° C. under an atmosphere of argon. The mixture was stirred for24 hours at room temperature. The reaction mixture was diluted withethyl acetate, washed, dried over and concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(hexane-AcOEt) to give the title compound (207 mg) having the followingphysical data.

TLC: Rf 0.50 (hexane:AcOEt=3:1); NMR: δ 8.07 (2H, d), 7.67 (2H, d), 7.58(1H, d), 7.49 (2H, d), 7.39 (1H, d), 7.34 (2H, d), 7.32 (1H, dd), 7.07(1H, brs), 3.96 (3H, s).

EXAMPLE 144-[2-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenyl]ethynyl]benzoicAcid

By using methyl4-[2-[2-(4-chlorophenylsulfonylamino)-5-chlorophenyl]ethynyl]benzoate(199 mg; prepared in Example 13.), the title compound (181 mg) havingthe following physical data was obtained by the same procedure asExample 2.

TLC: Rf 0.43 (CHCl₃:MeOH:ACOH=100:5:1); NMR (DMSO-d₆): δ 13.16 (1H,brs), 10.32 (1H, brs), 8.00 (2H, d), 7.65 (2H, d), 7.59 (1H, d), 7.57(2H, d), 7.50 (1H, dd), 7.43 (2H, d), 7.35 (1H, d).

REFERENCE EXAMPLE 17 Methyl4-(2-Amino-5-trifluoromethylphenoxymethyl)benzoate

By using 2-nitro-5-trifluoromethylphenol, the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 6→Reference Example 12.

TLC: Rf 0.33 (hexane:AcOEt=3:1).

EXAMPLE 15 Methyl4-(2-Phenylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate

By using methyl 4-(2-amino-5-trifluoromethylphenoxymethyl)benzoate(prepared in Reference Example 17.), the title compound having thefollowing physical data was obtained by the same procedure as Example 7.

TLC: Rf 0.76 (benzene:acetone=9:1); NMR: δ 8.05 (2H, d, J=8.2 Hz), 7.77(2H, m), 7.69 (1H, d, J=8.6 Hz),7.58 (1H, m), 7.45 (2H, m), 7.25 (3H,m), 7.18 (1H, m), 6.99 (1H, m), 5.02 (2H, s), 3.95 (3H, s).

EXAMPLE 164-(2-Phenylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoic Acid

By using methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate(prepared in Example 15.), the title compound having the followingphysical data was obtained by the same procedure as Example 2.

TLC: Rf 0.52 (CHCl₃:MeOH:AcOH=100:5:1); NMR (DMSO-d₆): δ 12.95 (1H,brd), 10.10 (1H, brd), 7.93 (2H, d, J=8.0 Hz), 7.75 (2H, m), 7.59 (1H,m), 7.40-7,53 (5H, m), 7.27 (2H, m), 5.14 (2H, s).

EXAMPLE 17 Methyl4-[2-(N-Isopropyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoate

To a solution of methyl4-(2-phenylsulfonylamino-4-chlorophenoxymethyl)benzoate (402 mg;prepared in Example 7(a).) in DMF (4 ml), potassium carbonate (256 mg)and isopropyl iodide (185 μl) were added. The mixture was stirredovernight at room temperature and for 9 hours at 50° C. To the reactionsolution, iced water and 2N HCl were added. The mixture was extractedwith ethyl acetate. The organic layer was washed, dried over,concentrated after filtration, solidified with ethanol and washed togive the title compound (411 mg) having the following physical data.

TLC: Rf 0.59 (hexane:AcOEt=2:1); NMR: δ 8.05 (2H, d, J=8.8 Hz),7.83-7.79 (2H, m), 7.55-7.26 (6H, m), 7.08 (1H, d, J=2.8 Hz), 6.89 (1H,d, J=8.8 Hz),5.04 (2H, s), 4.36 (1H, sept, J=6.8 Hz), 3,93 (3H, s), 1.05(6H, d, J=6.8 Hz).

EXAMPLE 17(1)-(4)

By using the corresponding compounds, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 6→Reference Example 7→Example 7→Example 17 or Reference Example8→Reference Example 9→Reference Example 10→Example 9→Example 17.

EXAMPLE 17(1) Methyl4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoate

TLC: Rf 0.55 (hexane:AcOEt=2:1); NMR: δ 8.07 (2H, d, J=8.4 Hz), 7.79(2H, m), 7.44-7.55 (3H, m), 7.32-7.43 (2H, m), 7.18-7.29 (3H, m), 5.10(2H, s), 4.38 (1H, sept, J=6.6 Hz), 3.94 (3H, s), 1.05 (6H, d, J=6.6Hz).

EXAMPLE 17(2) Methyl4-[2-(N-Isopropyl-phenylsulfonylamino)-5-methylphenoxymethyl]benzoate

TLC: Rf 0.48 (hexane:AcOEt=2:1); NMR: δ 8.04 (2H, d, J=8.4 Hz), 7.80(2H, m), 7.41-7.52 (3H, m), 7.28-7.39 (2H, m), 6.97 (1H, d, J=8.6 Hz),6.73-6.80 (2H, m), 5.00 (2H, s), 4.38 (1H, sept, J=7.0 Hz), 3.93 (3H,s), 2.35 (3H, s), 1.05 (6H, d, J=7.0 Hz).

EXAMPLE 17(3) Methyl4-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]benzoate

TLC: Rf 0.30 (hexane:AcOEt=4:1); NMR: δ 8.06 (2H, d, J=8.2 Hz), 7.78(2H, d, J=7.2 Hz), 7.25-7.48 (5H, m), 6.85-7.05 (3H, m), 5.02 (2H, s),4.37 (1H, sept, J=6.4 Hz), 3.94 (3H, s), 1.04 (6H, d, J=6.4 Hz).

EXAMPLE 17(4) Methyl4-[2-(N-Isopropyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamate

TLC: Rf 0.39 (benzene:AcOEt=19:1); NMR: δ 7.71 (1H, d, J=16 Hz),7.59-7.45 (5H, m), 7.23-7.20 (3H, m), 6.94-6.92 (1H, m), 6.50-6.42 (2H,m), 5.12 (2H, s), 4.5-4.4 (1H, m), 3.82 (3H, s), 1.09 (6H, dd, J=6.5, 2Hz).

EXAMPLE 184-[2-(N-Isopropyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoicAcid

By using methyl4-[2-(N-isopropyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoate(prepared in Example 17.), the title compound having the followingphysical data was obtained by the same procedure as Example 2.

TLC: Rf 0.43 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.90 (1H, br),7.94 (2H, d, J=8.4 Hz), 7.78 (2H, d, J=8.4 Hz), 7.66-7.45 (6H, m), 7.23(1H, d, J=8.4 Hz), 7.07 (1H, d, J=2.4 Hz), 5.13 (2H, s), 4.20 (1H, sept,J=6.6 Hz), 0.99 and 0.96 (each 3H, each d, J=6.6 Hz).

EXAMPLE 18(1)-18(128)

By using the corresponding compounds, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 6→Reference Example 7→Example 7→Example 17→Example 2 orReference Example 8→Reference Example 9→Reference Example 10→Example9→Example 17→Example 2.

EXAMPLE 18(1)4-[2-(N-Carboxymethylphenylsulfonylamino)-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.20 (CHCl₃:MeOH:H₂O=7:3:0.3); NMR (DMSO-d₆): δ 12.93 (2H, br),7.88 (2H, d, J=8.4 Hz), 7.63-7.37 (7H, m), 7.16-7.06 (3H, m), 4.88 (2H,s), 4.31 (2H, s).

EXAMPLE 18(2)4-[2-[N-(2-Hydroxyethyl)-phenylsulfonylamino]-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.26 (CHCl₃:MeOH H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.71 (1H, br),7.88 (2H, d, J=8.4 Hz), 7.63-7.32 (7H, m), 7.19-7.08 (3H, m), 4.89 (2H,brs), 4.71 (1H, br), 3.86-3.40 (4H, m).

EXAMPLE 18(3)4-[2-(N-Methylphenylsulfonylamino)-4-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.31 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.90 (1H, br),7.90 (2H, d, J=8.4 Hz), 7.76-7.70 (1H, dd-like), 7.64-7.43 (6H, m), 7.31(1H, d, J=8.4 Hz), 7.23 (2H, d, J=8.4 Hz), 5.05 (2H, s), 3.18 (3H, s).

EXAMPLE 18(4)4-[2-[N-(2-Hydroxyethyl)-phenylsulfonylamino]-4-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.24 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.51 (1H, br),7.89 (2H, d, J=8.4 Hz), 7.74 (1H, dd, J=2.2 and 8.4 Hz), 7.62-7.37 (6H,m), 7.28 (1H, d, J=8.4 Hz), 7.20 (2H, d, J=8.4 Hz), 5.00 (2H, brs), 4.70(1H, br), 3.66-3.28 (4H, m).

EXAMPLE 18(5)4-[2-[N-(2-Hydroxyethyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH:AcOH=100:5:1); NMR (DMSO-d₆): δ 12.96 (1H,brd), 7.89 (2H, d, J=8.4 Hz), 7.61 (2H, m), 7.34-7.58 (6H, m), 7.20 (2H,d, J=8.4 Hz), 5.05 (1H, brs), 4.67 (1H, m), 3.60 (2H, m), 3.42 (2H, m).

EXAMPLE 18(6)4-[2-(N-Methylphenylsulfonylamino)-5-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.36 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.63 (1H, br),7.89 (2H, d, J=8.4 Hz), 7.64-7.41 (5H, m), 7.25-7.19 (4H, m), 7.05 (1H,dd, J=2.2 and 8.4 Hz), 4.98 (2H, s), 3.12 (3H, s).

EXAMPLE 18(7)4-[2-[N-(2-Hydroxyethyl)-phenylsulfonylamino]-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.27 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-dB): δ 12.88 (1H, br),7.89 (2H, d, J=8.4 Hz), 7.62-7.36 (5H, m), 7.29-7.17 (4H, m), 7.06 (1H,dd, J=2.2 and 8.4 Hz), 4.95 (2H, brs), 4.68 (1H, br), 3.66-3.24 (4H,br).

EXAMPLE 18(8)4-[2-(N-Methylphenylsulfonylamino)-5-trifluoromethylphenoxymethy]benzoicAcid

TLC: Rf 0.46 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.08 (2H, d, J=8.0 Hz),7.68 (2H, m), 7.12-7.53 (8H, m), 4.93 (2H, s), 3.24 (3H, s).

EXAMPLE 18(9)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.44 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.15 (2H, d, J=8.6 Hz),7.81 (2H, m), 7.52 (3H, m), 7.38 (2H, m), 7.24 (3H, m), 5.13 (2H, s),4.40 (1H, sept, J=6.8 Hz), 1.06 (6H, d, J=6.8 Hz).

EXAMPLE 18(10)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.35 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.96 (1H, br),7.95 (2H, d, J=8.2 Hz), 7.78-7.74 (2H, m), 7.65-7.43 (5H, m), 7.32 (1H,s), 7.07 (2H, s), 5.21 and 5.07 (each 1H, each d, J=15.6 Hz), 4.21 (1H,sept-like), 0.94 (6H, d, J=6.8 Hz).

EXAMPLE 18(11)4-[2-(N-Isopropyl-phenylsulfonylamino)-4-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.30 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 13.03 (1H, br),7.95 (2H, d, J=8.2 Hz), 7.84-7.74 (3H, m), 7.67-7.39 (6H, m), 7.25 (1H,d, J=2.4 Hz), 5.28 and 5.21 (each 1H, each d, J=16.6 Hz), 4.26 (1H,sept-like), 0.98 and 0.97 (each 3H, each d, J=6.6 Hz).

EXAMPLE 18(12)4-[2-[N-(2-Methoxyethoxymethyl)-phenylsulfonylamino]-4-chIorphenoxymethyl]benzoicAcid

TLC: Rf 0.40 (CHCl₃:MEOH:H₂O 9:10.1); NMR (DMSO-d₆): δ 12.98 (1H, br),7.91 (2H, d, J=8.2 Hz), 7.66-7.52 (3H, m), 7.45-7.38 (3H, m), 7.26-7.22(3H, m), 7.10 (1H, d, J=8.2 Hz), 5.06 (2H, brs), 4.92 (2H, brs),3.68-3.63 (2H, t-like), 3.42-3.37 (2H, t-like), 3.21 (3H, s).

EXAMPLE 18(13)4-[2-[N-(2-Methoxyethyl)-phenylsulfonylamino]-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.25 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.92 (1H, br),7.88 (2H, d, J=8.2 Hz), 7.64-7.39 (6H, m), 7.22-7.10 (4H, m), 4.91 (2H,brs), 3.69 (2H, br), 3.38-3.33 (2H, m), 3.13 (3H, s).

EXAMPLE 18(14)4-[2-[N-[2-(2-Methoxyethoxy)ethyl]-phenylsulfonylamino]-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.29 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR (DMSO-d₆): δ 12.95 (1H, br),7.89 (2H, d, J=8.2 Hz), 7.65-7.39 (6H, m), 7.25 (1H, d, J=2.6 Hz), 7.20(2H, d, J=8.2 Hz), 7.11 (1H, d, J=8.2 Hz), 4.92 (2H, brs), 3.69 (2H,br), 3.47-3.28 (6H, m), 3.19 (3H, s).

EXAMPLE 18(15)4-[2-(N-Ethylphenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.51 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.2 Hz), 7.8-7.6(2H, m), 7.5-7.2 (7H, m), 6.81 (1H, d, J=9.4 Hz), 4.88 (2H, s), 3.67(2H, q, J=7.0 Hz), 1.11 (3H, t, J=7.0 Hz).

EXAMPLE 18(16)4-[2-(N-Propyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.50 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.4 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 6.80 (1H, d, J=9.6 Hz), 4.85 (2H, s), 3.6-3.5(2H, m), 1.6-1.4 (2H, m), 0.89 (3H, t, J=7.2 Hz).

EXAMPLE 18(17)4-[2-(N-Butyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.53 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.4 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 6.80 (1H, d, J=9.4 Hz), 4.86 (2H, S), 3.7-3.5(2H, m), 1.5-1.2 (4H, m), 0.85 (3H, t, J=7.0 Hz).

EXAMPLE 18(18)4-[2-(N-Pentyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.56 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.2 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 6.8-6.7 (1H, m), 4.86 (2H, s), 3.6-3.5 (2H,m), 1.5-1.2 (6H, m), 0.9-0.8 (3H, m).

EXAMPLE 18(19)4-[2-(N-Hexyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.58 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.6 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 6.9-6.8 (1H, m), 4.86 (2H, s), 3.6-3.5 (2H,m), 1.5-1.1 (8H, m), 0.9-0.8 (3H, m).

EXAMPLE 18(20)4-[2-(N-Benzyl-phenyIsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.60 (CHCl₃:MeOH=9:1); NMR: δ 8.09 (2H, d, J=8.6 Hz), 7.8-7.7(2H, m), 7.6-7.3 (3H, m), 7.3-7.1 (9H, m), 6.71 (1H, d, J=8.8 Hz), 4.82(2H, s), 4.78 (2H, s).

EXAMPLE 18(21)4-[2-(N-isopropyl-phenylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.50 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.13 (2H, d, J=8.2 Hz),7.82 (2H, m), 7.49 (3H, m), 7.36 (2H, m), 6.98 (1H, d, J=8.6 Hz), 6.77(2H, m), 5.05 (2H, s), 4.40 (1H, sept, J=6.6 Hz), 2.36 (3H, s), 1.05(6H, d, J=6.6 Hz).

EXAMPLE 18(22)4-[2-(N-Methylphenylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.56 (AcOEt:hexane:ACOH=9:10:1); NMR (DMSO-d₆): δ 12.96 (1H,brs), 7.89 (2H, d, J=8.5 Hz), 7.67-7.40 (5H, m), 7.23 (2H, d, J=8.0 Hz),7.06 (1H, d, J=8.0 Hz), 6.93 (1H, s), 6.78 (1H, d, J=8.0 Hz), 4.93 (2H,s), 3.12 (3H, s), 2.30 (3H, s).

EXAMPLE 18(23) 4-[2-[N-(2-Hydroxyethyl)-phenylsulfonylamino]-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.27 (AcOEt:hexane:AcOH=9:10:1); NMR (DMSO-d₆): δ 12.95 (1H,brs), 7.87 (2H, d, J=8.5 Hz), 7.55-7.32 (5H, m), 7.20 (2H, d, J=8.5 Hz),7.08 (1H, d, J=8.0 Hz), 6.91 (1H, s), 6.77 (1H, d, J=8.0 Hz), 4.89 (2H,brs), 4.63 (1H, t, J=4.0 Hz), 3.50-3.20 (4H, m), 2.29 (3H, s).

EXAMPLE 18(24)4-[2-[N-(Prop-2-enyl)-phenylsulfonylamino]-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.54 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.0 Hz), 7.8-7.6(2H, m), 7.6-7.2 (7H, m), 6.78 (1H, d, J=9.4 Hz), 5.9-5.6 (1H, m),5.2-5.0 (2H, m), 4.86 (2H, s), 4.3-4.2 (2H, m).

EXAMPLE 18(25)4-[2-(N-Cyclopentyl-phenyfsulfonylamino)-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 8.13 (2H, d, J=8.4 Hz), 7.9-7.8(2H, m), 7.6-7.2 (6H, m), 7.07 (1H, d, J=2.6 Hz), 6.88 (1H, d, J=8.8Hz), 5.1-5.0 (2H, m), 4.5-4.3 (1H, m), 2.0-1.7 (2H, m), 1.6-1.2 (6H, m).

EXAMPLE 18(26)4-[2-[N-(2-Methoxyethyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.46 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.07 (2H, d, J=8.4 Hz),7.66 (2H, m), 7.18-7.53 (7H, m), 7.12 (1H, m), 4.90 (2H, s), 3.81 (2H,m), 3.51 (2H, t, J=6.0 Hz), 3.24 (3H, s).

EXAMPLE 18(27)4-[2-(N-Ethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH=9:1); NMR: δ 8.09 (2H, d, J=8.4 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 7.15 (1H, d, J=1.6 Hz), 4.94 (2H, s), 3.69(2H, q, J=7.4 Hz), 1.11 (3H, t, J=7.4 Hz).

EXAMPLE 18(28)4-[2-(N-Propyl-phenylsulfonylamino)-S-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.5 (CHCl₃:MEOH=9:1); NMR: δ 8.09 (2H, d, J=8.2 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 7.14 (1H, s), 4.92 (2H, s), 3.59 (2H, t, J=7.4Hz), 1.6-1.4 (2H, m), 0.88 (3H, t, J=7.4 Hz).

EXAMPLE 18(29)4-[2-(N-Isobutyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.53 (CHCl₃:MeOH=9:1); NMR: δ 8.10 (2H, d, J=8.4 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 7.11 (1H, d, J=1.6 Hz), 5.0-4.8 (2H, m), 3.44(2H, d, J=7.4 Hz), 1.7-1.5 (1H, m), 0.90 (6H, d, J=6.4 Hz).

EXAMPLE 18(30)4-[2-(N-Cyclopentyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.54 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.0 Hz), 7.8-7.7(2H, m), 7.6-7.3 (5H, m), 7.3-7.2 (3H, m,), 5.2-5.0 (2H, m), 4.5-4.3(1H, m), 2.0-1.8 (2H, m), 1.6-1.2 (6H, m).

EXAMPLE 18(31)4-[2-[N-(Prop-2-enyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 8.10 (2H, d, J=8.6 Hz); 7.8-7.6(2H, m), 7.6-7.2 (7H, m), 7.12 (1H, s), 5.9-5.6 (1H, m), 5.1-5.0 (2H,m), 4.93 (2H, s), 4.24 (2H, d, J=6.2 Hz).

EXAMPLE 18(32)4-[2-[N-(2-Methylprop-2-enyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.48 (CHCl₃:MeOH=9:1); NMR: δ 8.10 (2H, d, J=8.4 Hz), 7.7-7.6(2H, m), 7.5-7.2 (7H, m), 7.10 (1H, s), 4.89 (2H, s), 4.71 (2H, d,J=12.0 Hz), 4.20 (2H, s), 1.74 (3H, s).

EXAMPLE 18(33)4-[2-(N-Isopropyl-4-methylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.60 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.14 (2H, d, J=8.4 Hz),7.68 (2H, d, J=8.2 Hz), 7.52 (2H, d, J=8.2 Hz), 7.19 (5H, m, arom), 5.14(2H, s), 4.38 (1H, sept., J=6.8 Hz), 2.38 (3H, s), 1.05 (6H, d, J=6.8Hz).

EXAMPLE 18(34)4-[2-(N-Isopropyl-4-fluorophenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.60 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.16 (2H, d, J=8.2 Hz),7.76 (2H, m, arom), 7.52 (2H, d, J=8.2 Hz), 7.26 (3H, m, arom), 7.01(2H, m, arom), 5.10 (2H, dd, J=11.8, 14.6 Hz), 4.38 (1H, sept., J=6.4Hz), 1.09 (3H, d, J=6.4 Hz), 1.07 (3H, d J=6.4 Hz).

EXAMPLE 18(35)4-[2-(N-Isopropyl-4-methoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.60 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.15 (2H, d, J=8.2 Hz),7.72 (2H, d, J=8.8 Hz), 7.53 (2H, d, J=8.2 Hz), 7.18 (3H, m, arom), 6.81(2H, d, J=9.2 Hz), 5.14 (2H, s), 4.35 (1H, sept., J=6.4 Hz), 3.83 (3H,s), 1.08 (3H, d, J=6.4 Hz), 1.05 (3H, d, J=6.4 Hz).

EXAMPLE 18(36)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxy]benzoic Acid

TLC: Rf 0.36 (CHCl₃:MeOH=9:1); NMR: δ 8.11 (2H, d, J=8.6 Hz), 7.8-7.7(2H, m), 7.6-7.3 (3H, m), 7.2-7.1 (2H, m), 7.02 (2H, d, J=8.6 Hz), 6.92(1H, d, J=2.0 Hz), 4.6-4.4 (1H, m), 1.14 (3H, d, J=2.4 Hz), 1.11 (3H, d,J=2.4 Hz).

EXAMPLE 18(37)3-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxy]cinnamic Acid

TLC: Rf 0.33 (CHCl₃:MeOH=9:1); NMR: δ 7.9-7.8 (2H, m), 7.73 (1H, d,J=15.8 Hz), 7.6-7.3 (5H, m), 7.2-7.0 (4H, m), 6.78 (1H, d, J=2.2 Hz),6.42 (1H, d, J=15.8 Hz), 4.6-4.4 (1H, m), 1.17 (3H, d, J=6.8 Hz), 1.13(3H, d, J=6.8 Hz).

EXAMPLE 18(38)trans-4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cyclohexanoicAcid

TLC: Rf 0.53 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.81 (2H, m), 7.42-7.63(3H, m), 7.10-7.24 (3H, m), 4.38 (1H, sept, J=6.8 Hz), 3.79 (2H, m),2.33 (1H, tt, J=3.8, 10.2 Hz), 2.11 (2H, m), 1.93 (2H, m), 1.71 (1H, m),1.50 (2H, m), 1.18 (2H, m), 1.07 (3H, d, J=6.8 Hz), 1.02 (3H, d, J=6.8Hz).

EXAMPLE 18(39)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxy]phenylacetic Acid

TLC: Rf 0.43 (CHCl₃:MeOH=9:1); NMR: δ 7.9-7.8 (2H, m), 7.6-7.4 (3H, m),7.28 (2H, d, J=7.4 Hz), 7.13 (1H, d, J=8.6 Hz), 7.01 (1H, dd, J=2.2, 8.6Hz), 6.89 (2H, d, J=8.6 Hz), 6.78 (1H, d, J=2.2 Hz), 4.6-4.4 (1H, m),3.66 (2H, s), 1.15 (3H, s), 1.12 (3H, s).

EXAMPLE 18(40)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.5 (CHCl₃:MeOH=9:1); NMR: δ 7.9-7.8 (3H, m), 7.60 (2H, d, J=8.0Hz), 7.5-7.3 (5H, m), 7.3-7.2 (3H, m), 6.49 (1H, d, J=15.8 Hz), 5.08(2H, s), 4.4-4.3 (1H, m), 1.05 (6H, d, J=6.6 Hz).

EXAMPLE 18(41)3-[4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-phenyl]propionicAcid

TLC: Rf 0.59 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (2H, d, J=7.4 Hz), 7.5-7.4(1H, m), 7.4-7.2 (9H, m), 4.99 (2H, s), 4.4-4.2 (1H, m), 3.00 (2H, t,J=7.6 Hz), 2.72 (2H, t, J=7.6 Hz), 1.08 (3H, d, J=6.8 Hz), 1.02 (3H, d,J=6.8 Hz).

EXAMPLE 18(42)3-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]phenylaceticAcid

TLC: Rf 0.50 (CHCl₃:MeOH=9:1); NMR: δ 7.8-7.7 (2H, m), 7.6-7.2 (10H, m),5.05 (1H, d, J=11.0 Hz), 4.98 (1H, d, J=11.0 Hz), 4.4-4.2 (1H, m), 3.68(2H, s), 1.06 (3H, d, J=6.6 Hz), 1.03 (3H, d, J=6.6 Hz).

EXAMPLE 18(43)4-[2-(N-Isopropyl-4-ethoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.44 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.2 Hz), 7.71 (2H,d, J=8.8 Hz), 7.54 (2H, d, J=8.2 Hz), 7.3-7.2 (3H, m), 6.78 (2H, d,J=8.8 Hz), 5.14 (2H, s), 4.4-4.2 (1H, m), 4.03 (2H, q, J=7.0 Hz), 1.44(3H, t, J=7.0 Hz), 1.08 (3H, d, J=7.0 Hz), 1.04 (3H, d, J=7.0 Hz).

EXAMPLE 18(44)4-[2-(N-Isobutyl-phenylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.47 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.07 (2H, d, J=8.2 Hz),7.63 (2H, m), 7.15-7.44 (6H, m), 6.79 (1H, m), 6.65 (1H, m), 4.80 (2H,m), 3.40 (2H, m), 2.33 (3H, s), 1.63 (1H, m), 0.90 (6H, d, J=6.4 Hz).

EXAMPLE 18(45)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-fluorophenoxymethyl]benzoicAcid

TLC: Rf 0.33 (CHCl₃:MeOH=20:1); NMR: (DMSO-d₆): δ 7.95 (2H, d, J=8.2Hz), 7.80 (2H, d, J=7.2 Hz), 7.46-7.65 (5H, m), 7.08 (2H, m), 6.82 (1H,m), 5.14 (2H, bs), 4.20 (1H, sept, J=6.6 Hz), 0.94 (6H, d, J=6.6 Hz).

EXAMPLE 18(46)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-methoxyphenoxymethyl]benzoicAcid

TLC: Rf 0.30 (CHCl₃:MeOH=20:1); NMR: (DMSO-d₆): δ 7.95 (2H, d, J=8.2Hz), 7.73 (2H, d, J=7.2 Hz), 7.42-7.68 (3H, m), 6.93 (2H, d, J=8.6 Hz),7.21 (1H, m), 6.56 (2H, dd, J=8.6 Hz, J=2.8 Hz), 5.11 (2H, bs), 4.20(1H, sept, J=6.6 Hz), 3.79 (3H, s), 0.94 (6H, d, J=6.6 Hz).

EXAMPLE 18(47)4-[2-(N-Propyl-phenylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.38 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.07 (2H, d, J=8.6 Hz),7.67 (2H, m), 7.15-7.45 (6H, m), 6.79 (1H, m), 6.68 (1H, m), 4.83 (2H,brs), 3.57 (2H, m), 2.34 (3H, s), 1.48 (2H, m), 0.88 (3H, t, J=7.4 Hz).

EXAMPLE 18(48)4-[(2-[N-(Prop-2-enyl)-phenylsulfonylamino]-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.39 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.07 (2H, d, J=8.0 Hz),7.69 (2H, m), 7.13-7.48 (6H, m), 6.78 (1H, m), 6.66 (1H, m), 5.80 (1H,tdd, J=6.2, 10.2, 17.2 Hz), 4.98-5.12 (2H, m), 4.84 (2H, brs), 4.23 (2H,m), 2.33 (3H, s).

EXAMPLE 18(49)4-[2-[N-(2-Methylprop-2-enyl)-phenylsulfonylamino]-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.37 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.07 (2H, d, J=8.2 Hz),7.66 (2H, m), 7.16-7.47 (6H, m), 6.77 (1H, m), 6.64 (1H, m), 4.80 (2H,brs), 4.71 (2H, m), 4.20 (1H, brs), 2.32 (3H, s), 1.77 (3H, s).

EXAMPLE 18(50)4-[2-(N-Cyclopropylmethylphenylsulfonylamino)-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.31 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.06 (2H, d, J=8.0 Hz),7.68 (2H, m), 7.18-7.44 (6H, m), 6.80 (1H, m), 6.68 (1H, m), 4.84 (2H,brs), 3.48 (2H, m), 2.34 (3H, s), 0.91 (1H, m), 0.38 (2H, m), 0.07 (2H,m).

EXAMPLE 18(51)4-[2-(N-Propyl-phenylsulfonylamino)-5-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.32 (CHCl₃:MeOH=20:1); NMR: δ 8.07 (2H, d, J=7.8 Hz), 7.64 (2H,d, J=6.8 Hz), 7.10-7.41 (6H, m), 6.85-6.99 (2H, m), 4.82 (2H, bs), 3.55(2H, t, J=6.8 Hz), 1.35-1.52 (2H, m), 0.87 (3H, t, J=7.6 Hz).

EXAMPLE 18(52)4-[2-(N-Isobutyl-phenylsulfonylamino)-5-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.32 (CHCl₃:MeOH=20:1); NMR: δ 8.04 (2H, d, J=7.8 Hz), 7.54 (2H,d, J=7.4 Hz), 7.10-7.41 (6H, m), 6.80-7.01 (2H, m), 4.58-4.95 (2H, bs),3.34 (2H, d, J=7.0 Hz), 1.46-1.65 (1H, m), 0.83 (6H, d, J=6.4 Hz).

EXAMPLE 18(53)4-[2-[N-(Prop-2-enyl)-phenylsulfonylamino]-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.30 (CHCl₃:MeOH=20:1); NMR: δ 8.09 (2H, d, J=8.2 Hz), 7.68 (2H,d, J=6.8 Hz), 7.19-7.52 (6H, m), 6.87-7.01 (2H, m), 5.76 (1H, ddt, J=17.2 Hz, 9.8 Hz, 6.4 Hz) 5.09 (1H, d, J=17.2 Hz), 5.07 (1H, d, J=9.8 Hz),4.85 (2H, s), 4.21 (2H, d, J=6.4 Hz).

EXAMPLE 18(54)4-[2-[N-(2-Methylprop-2-enyl)-phenylsulfonylamino]-5-chlorophenoxymethyl]-benzoicAcid

TLC: Rf 0.33 (CHCl₃:MeOH=20:1); NMR: δ 8.09 (2H, d, J=8.2 Hz), 7.65 (2H,d, J=6.8 Hz), 7.21-7.51 (6H, m), 6.83-7.00 (2H, m), 4.81(2H, s), 4.74(1H, s), 4.68 (1H, s), 4.18 (2H,s), 1.75 (3H, s).

EXAMPLE 18(55)4-[2-(N-Cyclopropylmethylphenylsulfonylamino)-5-chlorophenoxymethyl]-benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=20:1); NMR: δ 8.07 (2H, d, J=8.6 Hz), 7.69 (2H,d, J=7.0 Hz), 7.20-7.48 (6H, m), 6.85-7.09 (2H, m), 4.85(2H, s), 3.47(2H, bs), 0.85 (1H, m), 0.38 (2H, m), 0.06 (2H, m).

EXAMPLE 18(56)5-[2-(N-Isopropyl-phenylsulfonylamino)-5-methylphenoxymethyl]furan-2-carboxylicAcid

TLC: Rf 0.18 (CHCl₃:MeOH=9:1); NMR: δ 7.82 (2H, m), 7.56-7.35 (3H, m),7.31 (1H, d, J=3.5 Hz), 6.97 (1H, d, J=8.5 Hz), 6.83-6.75 (2H, m), 6.63(1H, d, J=3.5 Hz), 5.03 (1H, d, J=14 Hz, 4.98 (1H, d, J=14 Hz), 4.37(1H, m), 2.37 (3H, s), 1.09-0.96 (6H, m).

EXAMPLE 18(57)4-[2-(N-Methoxymethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.45 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.09 (2H, d, J=8.0 Hz),7.65 (2H, m), 7.43-7.53 (2H, m), 7.20-7.40 (5H, m), 7.11 (1H, m), 5.09(2H, s), 4.89 (2H, s), 3.44 (3H, s).

EXAMPLE 18(58)4-[2-(N-Isopropyl-2-thienylsulfonylamino)-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.34 (CHCl₃:MeOH=20:1); NMR: δ 8.14 (2H, d, J=8.2 Hz), 7.52-7.57(4H, m), 6.98-7.03 (4H, m), 5.12 (2H, s), 4.55 (1H, sept, J=6.4 Hz),1.09 (6H, d, J=6.6 Hz).

EXAMPLE 18(59)4-[2-(N-Isopropyl-2-thienylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.39 (CHCl₃:MeOH 20:1); NMR: δ 8.13 (2H, d, J=8.2 Hz), 7.43-7.58(4H, m), 6.97 (1H, m), 6.80 (2H, m), 5.12 (2H, s), 4.45 (1H, sept, J=6.4Hz), 1.09 (6H, d, J=6.6 Hz).

EXAMPLE 18(60)4-[2-(N-Isopropyl-2-furanylsufonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.42 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.14 (2H, d, J=8.2 Hz),7.58 (2H, d, J=8.2 Hz), 7.44 (1H, dd, J=0.8, 1.6 Hz), 6.88-6.95 (2H, m),6.72-6.82 (2H, m), 6.41 (1H, dd, J=1.6, 3.4 Hz), 5.12 (2H, s), 4.51 (1H,sept, J=6.6 Hz), 2.31 (3H, s), 1.12 (3H, d, J=6.6 Hz), 1.10 (3H, d,J=6.6 Hz).

EXAMPLE 18(61)4-[2-(N-Isopropyl-2-furanylsufonylamino)-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.16 (2H, d, J=8.4 Hz),7.57 (2H, d, J=8.4 Hz), 7.45 (1H, dd, J=0.8, 1.6 Hz), 6.95-7.04 (3H, m),6.92 (1H, d, J=4.4 Hz), 6.43 (1H, dd, J=1.8, 3.4 Hz) 5.13 (2H, s), 4.49(1H, sept, J=7.0 Hz), 1.11 (3H, d, J=7.0 Hz), 1.09 (3H, d, J=7.0 Hz).

EXAMPLE 18(62)4-[2-(N-Isobutyl-phenylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.23 (hexane:AcOEt=1:1); NMR: δ 8.06 (2H, d, J=8 Hz), 7.65-7.61(2H, m), 7.6-7.4 (7H, m), 6.71 (1H, d, J=8 Hz), 4.9-4.6 (2H, m), 3.5-3.4(2H, m), 2.29 (3H, s), 1.63 (1H, sept., J=6.5 Hz), 0.91 (6H, d, J=6.5Hz).

EXAMPLE 18(63)4-[2-(N-Isopropyl-phenylsulfonylamino)-4-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.22 (hexane:AcOEt=1:1); NMR: δ 8.12 (2H, d, J=8 Hz), 7.86-7.81(2H, m), 7.52-7.30 (5H, m), 7.15-7.10 (1H, m), 6.94 (1H, d, J=1.5 Hz),6.84 (1H, d, J=6 Hz), 5.02 (2H, s), 4.37 (1H, sept., J=6.5 Hz), 2.28(3H, s), 1.08 (6H, t, J=6.5 Hz).

EXAMPLE 18(64)4-[2-[N-(Prop-2-enyl)-phenylsulfonylamino]-4-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH:AcOH=100:5:1); NMR: (DMSO-d₆): δ 7.89 (2H, d,J=8.2 Hz), 7.63 (2H, m), 7.38-7.59 (3H, m), 7.23 (2H, d, J=8.2 Hz), 7.12(1H, dd, J=1.8, 8.4 Hz), 6.98 (1H, d, J=1.8 Hz), 6.94 (1H, d, J=8.6 Hz),5.71 (1H, tdd, J=6.4, 10.0, 17.2 Hz), 4.97-5.13 (2H, m), 4.88 (2H, brs),4.17 (2H, m), 2.22 (3H, s).

EXAMPLE 18(65)4-[2-(N-Isopropyl-4-ethoxyphenylsulfonylamino)-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.33 (CHCl₃:MeOH=20:1); NMR: δ 8.13 (2H, d, J=8.6 Hz), 7.69 (2H,d, J=9.0 Hz), 7.49 (2H, d, J=8.6 Hz), 6.97-7.09 (3H, m), 6.76 (2H, d,J=9.0 Hz), 5.06 (2H, s), 4.34 (1H, sept, J=6.6 _(Hz),) 4.02 (2H, q,J=7.2 Hz), 1.43 (3H, t, J=7.0 Hz), 1.06 (3H, d, J=6.6 Hz), 1.03 (3H, d,J=6.6 Hz).

EXAMPLE 18(66)4-[2-(N-Isopropyl-4-ethoxyphenylsulfonylamino)-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.29 (CHCl₃:MeOH=20:1); NMR: δ 8.12 (2H, d, J=8.4 Hz), 7.72 (2H,d, J=8.6 Hz), 7.50 (2H, d, J=8.6 Hz), 7.01 (1H, d, J=8.8 Hz), 6.72-6.80(4H, m), 5.07 (2H, s), 4.34 (1H, sept, J=6.6 Hz), 4.01 (2H, q, J=7.0Hz), 2.36 (3H, s), 1.42 (3H, t, J=6.8 Hz), 1.07 (3H, d, J=7.2 Hz), 1.04(3H, d, J=6.8 Hz).

EXAMPLE 18(67)4-[2-(N-Ethylphenylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.33 (CHCl₃:MeOH=9:1); NMR: δ 8.05 (2H, d, J=8.4 Hz), 7.8-7.6(2H, m), 7.4-7.2 (5H, m), 7.2-7.0 (2H, m), 6.75 (1H, d, J=8.4 Hz), 4.82(2H, s), 3.8-3.6 (2H, m), 2.30 (3H, s),1.11 (3H, t, J=7.0 Hz).

EXAMPLE 18(68)4-[2-(N-Propyl-phenylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.44 (CHCl₃:MeOH=9:1); NMR: δ 8.05 (2H, d, J=8.0 Hz), 7.7-7.6(2H, m), 7.5-7.0 (7H, m), 6.74 (1H, d, J=8.4 Hz), 4.80 (2H, s), 3.7-3.5(2H, m), 2.29 (3H, s), 1.6-1.4 (2H, m), 0.89 (3H, t, J=7.4 Hz).

EXAMPLE 18(69)4-[2-(N-Butyl-phenylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 8.05 (2H, d, J=8.2 Hz), 7.7-7.6(2H, m), 7.4-7.2 (5H, m), 7.2-7.0 (2H, m, 6.74 (1H, d, J=8.4 Hz), 4.80(2H, s), 3.7-3.5 (2H, m), 2.30 (3H, s), 1.6-1.2 (4H, m), 0.85 (3H, t,J=7.0 Hz).

EXAMPLE 18(70)4-[2-[N-(2-Methylprop-2-enyl)-phenylsulfonylamino]-4-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.38 (CHCl₃:MeOH=9:1); NMR: δ 8.06 (2H, d, J=8 Hz), 7.65 (2H,m), 7.47-7.25 (3H, m), 7.19 (2H, d, J=8 Hz), 7.13 (1H, d, J=2 Hz), 7.04(1H, dd, J=8 and 2 Hz), 6.70 (1H, d, J=8 Hz), 4.85-4.65 (4H, m), 4.21(2H, s), 2.29 (3H, s), 1.78 (3H, s).

EXAMPLE 18(71)4-[2-(N-Cyclopropylmethylphenylsulfonylamino)-4-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH:AcOH=100:5:1); NMR (CD₃COCD₃): δ 7.99(2H, d,J=8.0 Hz), 7.68 (2H, m), 7.26-7.57 (5H, m), 7.15 (2H, m), 6.96 (1H, d,J=8.8 Hz), 4.93 (2H, brs), 3.52 (2H, brd, J=7.0 Hz), 2.28 (3H, s), 0.90(1H, m), 0.35 (2H, m), 0.06 (2H, m).

EXAMPLE 18(72)4-[2-(N-Isopropyl-propylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.24 (CHCl₃:MeOH=19:1); NMR: δ 8.14 (2H, d, J=8.2 Hz), 7.57 (2H,d, J=8.2 Hz), 7.16 (1H, m), 6.82 (2H, m), 5.13 (2H, s), 4.33 (1H, m),2.97 (2H, m), 2.36 (3H, s), 1.79 (2H, m), 1.23 (3H, d, J=6.6 Hz), 1.09(3H, d, J=6.6 Hz), 0.85 (3H, t, J=7.4 Hz).

EXAMPLE 18(73)4-[2-(N-Isopropyl-pentylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.26 (CHCl₃:MeOH 19:1); NMR: δ 8.15 (2H, d, J=8.0 Hz), 7.56 (2H,d, J=8.0 Hz), 7.14 (1H, m), 6.81 (2H, m), 5.12 (2H, s), 4.32 (1H, m),2.97 (2H, m), 2.36 (3H, s), 1.77 (2H, m), 1.24 (3H, d, J=6.6 Hz), 1.16(4H, m), 1.09 (3H, d, J=6.6 Hz), 1.12 (3H, d, J=6.6 Hz), 0.83 (3H, t,J=6.4 Hz).

EXAMPLE 18(74)4-[2-(N-Benzyl-methylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.39 (CHCl₃:MeOH=19:1); NMR: δ 8.17 (2H, d, J=8.0 Hz), 7.53 (2H,d, J=8.0 Hz), 7.25 (5H, s), 6.98 (1H, m), 6.77 (2H, m), 5.17 (2H, s),4.70 (2H, bs), 2.89 (3H, s), 2.30 (3H, s).

EXAMPLE 18(75)4-[2-(N-Benzyl-propylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.40 (CHCl₃:MeOH=19:1); NMR: δ 8.17 (2H, d, J=8.2 Hz), 7.55 (2H,d, J=8.2 Hz), 7.23 (5H, s), 6.98 (1H, m), 6.78 (2H, m), 5.16 (2H, s),4.77 (2H, bs), 2.95 (2H, m), 2.29 (3H, s), 1.81 (2H, m), 0.85 (3H, t,J=7.6 Hz).

EXAMPLE 18(76)4-[2-(N-Isopropyl-cyclopentylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.38 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.15 (2H, d, J=8.0 Hz),7.59 (2H, d, J=8.0 Hz), 7.14 (1H, d, J=8.6 Hz), 6.81 (2H, m), 5.12 (2H,s), 4.35 (1H, sept, J=6.6 Hz), 3.51 (1H, m), 2.36 (3H, s), 1.85-2.15(3H, m), 1.61-1.85 (3H, m), 1.34-1.61 (2H, m), 1.22 (3H, d, J=6.6 Hz),1.08 (3H, d, J=6.6 Hz).

EXAMPLE 18(77)4-[2-(N-Isobutyl-ethylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.23 (hexane:AcOEt=1:1); NMR: δ 8.15 (2H, d, J=8 Hz), 7.53 (2H,d, J=8 Hz), 7.21 (1H, d, J=1.5 Hz), 7.08 (1H, dd, J=8.5, 1.5 Hz), 6.86(1H, d, J=8.5 Hz), 5.17 (2H, s), 3.46 (2H, d, J=7.5 Hz), 2.97 (2H, q,J=7.5 Hz), 2.30 (3H, s), 1.7-1.5 (1H, m), 1.25 (3H, t, J=7.5 Hz),0.94-0.90 (6H, m).

EXAMPLE 18(78)4-[2-(N-Isobutyl-propylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.27 (hexane:AcOEt=1:1); NMR: δ 8.15 (2H, d, J=8 Hz), 7.53 (2H,d, J=8 Hz), 7.20 (1H, d, J=0.5 Hz), 7.08 (1H, dd, J=8, 0.5 Hz), 6.86(1H, d, J=8 Hz), 5.17 (2H, s), 3.44 (2H, d, J=7 Hz), 2.94-2.86 (2H, m),2.30 (3H, s), 1.9-1.6 (3H, m), 1.0-0.9 (6H, m), 0.85 (3H, t, J=7 Hz).

EXAMPLE 18(79)4-[2-(N-Isobutyl-butylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.37 (hexane:AcOEt=1:1); NMR: δ 8.15 (2H, d, J=8 Hz), 7.53 (2H,d, J=8 Hz), 7.20 (1H, d, J=0.5 Hz), 7.08 (1H, dd, J=8.5, 0.5 Hz), 6.86(1H, d, J=8.5 Hz), 5.16 (2H, s), 3.45 (2H, d, J=7 Hz), 2.97-2.89 (2H,m), 2.30 (3H, s), 1.8-1.5 (3H, m), 1.3-1.1 (2H, m), 1.0-0.9 (6H, m),0.79 (3H, t, J=7 Hz).

EXAMPLE 18(80)4-[2-(N-Isobutyl-propylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.25 (CHCl₃:MeOH=20:1); NMR: δ 8.16 (2H, d, J=8.4 Hz), 7.53 (2H,d, J=8.4 Hz), 7.28 (1H, m), 6.82 (2H, m), 5.18 (2H, s), 3.41 (2H, d,J=7.0 Hz) 2.89 (2H, m), 2.35 (3H, s), 1.78 (2H, m), 1.60 (1H, m), 0.90(6H, d, J=7.0 Hz), 0.84 (3H, t, 7.6 Hz).

EXAMPLE 18(81)4-[2-[N-(Prop-2-enyl)-propylsulfonylamino]-5-methylphenoxymethy]benzoicAcid

TLC: Rf 0.23 (CHCl₃:MeOH=20:1); NMR: δ 8.16 (2H, d, J=8.4 Hz), 7.56 (2H,d, J=8.4 Hz), 7.21 (1H, m), 6.90 (2H, m), 5.80 (1H, m), 5.17 (2H, s),5.07 (2H, m), 4.21 (2H, d, J=6.2 Hz), 2.94 (2H, m), 2.34 (3H, s), 1.81(2H, m), 0.86 (3H, t, J=7.4 Hz).

EXAMPLE 18(82)4-[2-[N-(2-Methylprop-2-enyl)-propylsulfonylamino]-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.28 (CHCl₃:MeOH=20:1); NMR: δ 8.16 (2H, d, J=8.2 Hz), 7.54 (2H,d, J=8.2 Hz), 7.23 (1H, m), 6.78 (2H, m), 5.17 (2H, s), 4.75 (2H, s),4.18 (2H, s), 2.88 (2H, m), 2.34 (3H, s), 1.79 (2H, m), 1.78 (3H, s),0.85 (3H, t, J=7.6 Hz).

EXAMPLE 18(83)4-[2-(N-Isobutyl-phenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.29 (CHCl₃:MeOH=19:1); NMR: δ 8.06 (2H, d, J=8.0 Hz), 7.64 (2H,d, J=8.0 Hz), 7.20-7.40 (7H, m), 6.78 (1H, m), 4.80 (2H, bs), 3.40 (2H,d, J=7.0 Hz), 1.61 (1H, m), 0.90 (6H, d, J=7.0 Hz).

EXAMPLE 18(84)4-[2-(N-Propyl-propylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.52 (CHCl₃:MeOH=9:1); NMR: δ 8.17 (2H, d, J=8.4 Hz), 7.55 (2H,d, J=8.4 Hz), 7.25 (1H, d, J=8.2 Hz), 6.9-6.8 (2H, m), 5.17 (2H, s),3.56 (2H, t, J=7.4 Hz), 3.0-2.8 (2H, m), 2H, m), 2.35 (3H, s), 1.9-1.7(2H, m), 1.6-1.4 (2H, m), 0.89 (3H, t, J=7.2 Hz), 0.84 (3H, t, J=7.4Hz).

EXAMPLE 18(85)4-[2-(N-Isobutyl-hexylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 8.16 (2H, d, J=8.4 Hz), 7.53 (2H,d, J=8.4 Hz), 7.21 (1H, d, J=2.0 Hz), 7.09 (1H, dd, J=2.0, 8.4 Hz), 6.87(1H, d, J=8.4 Hz), 5.16 (2H, s), 3.45 (2H, d, J=7.0 Hz), 3.0-2.8 (2H,m), 2.30 (3H, s), 1.8-1.5 (3H, m), 1.3-1.0 (6H, m), 1.0-0.8 (6H, m),0.83 (3H, t, J=7.0 Hz).

EXAMPLE 18(86)4-[2-(N-Isobutyl-pentylsulfonylamino)-4-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.38 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.16 (2H, d, J=8.4 Hz),7.53 (2H, d, J=8.4 Hz), 7.21 (1H, d, J=2.2 Hz), 7.09 (1H, dd, J=2.2, 8.6Hz), 6.87 (1H, d, J=8.6 Hz), 5.16 (2H, s), 3.45 (2H, d, J=7.2 Hz), 2.91(2H, m), 2.30 (3H, s), 1.74 (2H, m), 1.60 (1H, m), 1.17 (4H, m), 0.92(6H, m), 0.82 (3H, m).

EXAMPLE 18(87)4-[2-[N-(Prop-2-enyl)-propylsulfonylamino]-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.33 (hexane:AcOEt=1:1); NMR (200 MHz, CDCl₃+1drop of CD₃OD): δ8.15-8.11 (2H, m), 7.54-7.44(3H, m), 7.30-7.24 (2H, m), 5.88-5.68 (1H,m), 5.20 (2H, s), 5.12-5.10 (1H, m), 5.04-5.03 (1H, m), 4.21 (2H, d,J=6.5 Hz), 2.95-2.87 (2H, m), 1.8-1.7 (1H, m), 0.84 (3H, t, J=7.5 Hz).

EXAMPLE 18(88)4-[2-[N-(2-Methylprop-2-enyl)-propylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.41 (hexane:AcOEt 1:1); NMR: δ 8.30 (2H, d, J=8 Hz), 7.71-7.67(2H, m), 7.62-7.56 (1H, m), 7.40-7.35 (2H, m), 5.34 (2H, s), 4.89-4.85(2H, m), 5.34 (2H, s), 4.89-4.85 (2H, m), 4.31 (2H, s), 3.07-2.99 (2H,m), 2.0-1.8 (2H, m), 1.87 (3H, s), 1.00-0.93 (3H, m).

EXAMPLE 18(89)4-[2-(N-Propyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.38 (hexane:AcOEt=1:1); NMR: δ 7.81 (1H, d, J=16 Hz), 7.59 (2H,d, J=8 Hz), 7.42-7.37 (3H, m), 7.28-7.24 (2H, m), 7.18 (1H, d, J=1.5Hz), 6.85 (1H, dd, J=3, 1 Hz), 6.49 (1H, d, J=16 Hz), 6.35 (1H, dd, J=3,2 Hz), 5.03 (2H, s), 3.71-3.64 (2H, m), 1.6-1.4 (2H, m), 0.88 (3H, t,J=7 Hz).

EXAMPLE 18(90)4[-(2-(N-Propyl-propylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=9:1); NMR: δ 8.17 (2H, d, J=8.2 Hz), 7.56 (2H,d, J=8.2 Hz), 7.49 (1H, m), 7.27 (2H, m), 5.22 (2H, s), 3.58 (2H, m),2.91 (2H, m), 1.79 (2H, m), 1.45 (2H, m), 0.89 (3H, t, J=7.4 Hz), 0.85(3H, t, J=7.6 Hz).

EXAMPLE 18(91)4-[2-(N-Isobutyl-propylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.45 (CHCl₃:MeOH=9:1); NMR: δ 8.18 (2H, d, J=8.2 Hz), 7.56 (2H,d, J=8.2 Hz), 7.51 (1H, m), 7.28 (2H, m), 5.23 (2H, s), 3.45 (2H, d,J=7.4 Hz), 2.89 (2H, m), 1.75 (2H, m), 1.58 (1H, m), 0.90 (6H, d, J=6.8Hz), 0.84 (3H, t, J=7.4 Hz).

EXAMPLE 18(92)4-[2-(N-Propyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.38 (hexane:AcOEt=1:1); NMR: δ 8.13 (2H, d, J=8 Hz), 7.44 (2H,d, J=8 Hz), 7.25 (1H, m), 7.12 (1H, d, J=8 Hz), 6.83-6.73 (3H, m),6.33-6.30 (1H, m), 5.01 (2H, s), 3.7-3.6 (2H, m), 2.33 (3H, s), 1.52(2H, q, J=7 Hz), 0.90 (3H, t, J=7 Hz).

EXAMPLE 18(93)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.41 (hexane:AcOEt=1:1); NMR: δ 8.13 (2H, d, J=8 Hz), 7.44 (2H,d, J=8 Hz), 7.25 (1H, m), 7.15 (1H, d, J=8 Hz), 6.80-6.71 (3H, m), 6.31(1H, m), 5.0 (2H, m), 3.53 (2H, d, J=7 Hz), 1.75-1.60(1H, m), 0.91 (6H,t, J=7 Hz).

EXAMPLE 18(94)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.44 (hexane:AcOEt=1:1); NMR: δ 7.81 (1H, d, J=16 Hz), 7.60 (2H,d, J=8 Hz), 7.41-7.37 (3H, m), 7.27-7.22 (2H, m), 7.17 (1H, m), 6.83(1H, dd, J=3.5, 1.5 Hz), 6.49 (1H, d, J=16 Hz), 6.35 (1H, dd, J=3.5, 1.5Hz), 5.02 (2H, s), 3.53 (2H, d, J=7.5 Hz), 1.74-1.50 (1H, m), 0.90 (6H,d, J=6.5 Hz).

EXAMPLE 18(95)4-[2-(N-Propyl-phenylsulfonylamino)-5-methylphenoxymethyl]cinnamic Acid

TLC: Rf 0.33 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.79 (1H, d, J=16.0 Hz),7.67 (2H, m), 7.51 (2H, d, J=8.0 Hz), 7.24-7.43 (3H, m), 7.17 (2H, d,J=8.0 Hz), 7.15 (1H, d, J=8.0 Hz), 6.78 (1H, m), 6.68 (1H, m), 6.47 (1H,d, J=16.0 Hz), 4.79 (2H, brs), 3.55 (2H, m), 2.34 (3H, s), 1.47 (2H, m),0.87 (3H, t, J=7.2 Hz).

EXAMPLE 18(96)4-[2-(N-Isobutyl-phenylsulfonylamino)-5-methylphenoxymethyl]cinnamicAcid

TLC: Rf 0.37 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.79 (1H, d, J=16.0 Hz),7.63 (2H, m), 7.51 (2H, d, J=8.2 Hz), 7.24-7.46 (3H, m), 7.18 (1H, d,J=7.8 Hz), 7.16 (2H, d, J=8.2 Hz), 6.78 (1H, m), 6.66 (1H, m), 6.48 (1H,d, J=16.0 Hz), 4.74 (2H, m), 3.41 (2H, m), 2.33 (3H, s), 1.61 (1H, m),0.89 (6H, d, J=6.4 Hz).

EXAMPLE 18(97)4-[2-(N-Isobutyl-propylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.36 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.80 (1H, d, J=16.0 Hz),7.62 (2H, d, J=8.4 Hz), 7.44-7.56 (3H, m), 7.24-7.33 (2H, m), 6.50 (1H,d, J=16.0 Hz), 5.17 (2H, s), 3.44 (2H, d, J=7.4 Hz), 2.87 (2H, m), 7.15(2H, m), 1.55 (1H, m), 0.90 (6H, d, J=6.6 Hz), 0.83 (3H, t, J=7.4 Hz).

EXAMPLE 18(98)4-[2-(N-Methylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.44 (CHCl₃:MeOH=9:1); NMR: δ 7.79 (1H, d, J=16.2 Hz), 7.7-7.6(2H, m), 7.6-7.2 (7H, m), 7.2-7.1 (3H, m), 6.49 (1H, d, J=16.2 Hz), 4.88(2H, s), 3.23 (3H, s).

EXAMPLE 18(99)4-[2-(N-Propyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.43 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.7-7.6(2H, m), 7.6-7.1 (10H, m), 6.49 (1H, d, J=16.0 Hz), 4.86 (2H, s), 3.57(2H, t, J=7.2 Hz), 1.6-1.3 (2H, m), 0.87 (3H, t, J=7.2 Hz).

EXAMPLE 18(100)4-[2-(N-Isobutyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.7-7.1(12H, m), 6.49 (1H, d, J=16.0 Hz), 4.9-4.7 (2H, br), 3.42 (2H, d, J=7.6Hz), 1.7-1.5 (1H, m), 0.89 (6H, d, J=6.6 Hz).

EXAMPLE 18(101)4-[2-(N-Isopropyl-propylsulfonylamino)-5-methylphenoxymethyl]cinnamicAcid

TLC: Rf 0.44 (CHCl₃:MeOH=9:1); NMR: δ 7.79 (1H, d, J=16.0 Hz), 7.53 (4H,m), 7.14 (1H, m), 6.80 (2H, m), 6.47 (1H, d, J=16.0 Hz), 5.07 (2H, s),4.31 (1H, m), 2.94 (2H, m), 1.79 (2H, m), 1.23 (3H, d, J=6.6 Hz), 1.08(3H, d, J=6.6 Hz), 0.83 (3H, t, J=7.2 Hz).

EXAMPLE 18(102)4-[2-(N-Ethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.37 (CHCl₃:MeOH=9:1); NMR: δ 7.79 (1H, d, J=16.0 Hz), 7.60-7.71(2H, m), 7.15-7.55 (10H, m), 6.49 (1H, d, J=16.0 Hz), 4.89 (2H, s), 3.67(2H, q, J=7.0 Hz), 1.09 (3H, t, J=7.0 Hz).

EXAMPLE 18(103)4-[2-(N-Cyclopropylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.14-7.55(10H, m), 7.67 (2H, m), 6.49 (1H, d, J=16.0 Hz), 4.88 (2H, s), 3.49 (2H,d, J=7.0 Hz), 0.87 (1H, m), 0.37 (2H, m), (2H, m)

EXAMPLE 18(104)4-[2-(N-Isopropyl-methylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 7.76 (1H, d, J=16.0 Hz), 7.61 (2H,d, J=8.4 Hz), 7.49 (2H, d, J=8.4 Hz), 7.37 (3H, m), 6.48 (1H, d, J=16.0Hz), 5.14 (2H, s), 4.31 (1H, m), 2.89 (3H, s), 1.28 (3H, d, J=6.6 Hz),1.09 (3H, d, J=6.6 Hz).

EXAMPLE 18(105)4-[2-(N-Benzyl-propylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.29 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.82 (1H, d, J=16.2 Hz),7.65 (2H, d, J=8.4 Hz), 7.51 (2H, d, J=8.4 Hz), 7.09-7.31 (8H, m), 6.52(1H, d, J=16.2 Hz), 5.17 (2H, s), 4.78 (2H, s), 2.94 (2H, m), 1.80 (2H,m), 0.85 (2H, t, J=7.4 Hz).

EXAMPLE 18(106)4-[2-(N-Propyl-phenylsulfonylamino)-4-methylphenoxymethyl]cinnamic Acid

TLC: Rf 0.39 (CHCl₃:MeOH=9:1); NMR: δ 7.79 (1H, d, J=16.0 Hz), 7.70-7.65(2H, m), 7.50 (2H, d, J=8.0 Hz), 7.42-7.38 (1H, m), 7.30 (2H, t, J=8.0Hz), 7.16 (2H, d, J=8.0 Hz), 7.11 (1H, d, J=1.5 Hz), 7.07 (1H, dd,J=1.5, 8.0 Hz), 6.74 (1H, d, J=8.0 Hz), 6.47 (1H, d, J=16.0 Hz),4.90-4.70 (2H, br), 3.70-3.50 (2H, br), 2.29 (3H, s), 1.55-1.45 (2H, m),0.88 (3H, t, J=7.0 Hz).

EXAMPLE 18(107)4-[2-[N-(Prop-2-enyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.35 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.71-7.68(2H, m), 7.54 (2H, d, J=8.0 Hz), 7.49-7.45 (1H, m), 7.40 (1H, d, J=8.0Hz), 7.38-7.33 (2H, m), 7.25 (1H, dd, J=2.0, 8.0 Hz), 7.19 (2H, d, J=8.0Hz), 7.12 (1H, d, J=2.0 Hz), 6.49 (1H, d, J=16.0 Hz), 5.80-5.70 (1H, m),5.07-5.02 (2H, m), 4.88 (2H, s), 4.5-4.3 (2H, m).

EXAMPLE 18(108)4-[2-[N-Methylprop-2enyl)-phenhylsulfolamino]-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.39 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.68-7.63(2H, m), 7.54 (2H, d, J=8.0 Hz), 7.48-7.44 (1H, m), 7.41 (1H, d, J=8.0Hz), 7.35 (2H, t, J=8.0 Hz), 7.25 (1H, dd, J=1.5, 8.0 Hz), 7.17 (2H, d,J=8.0 Hz), 7.10 (1H, d, J=1.5 Hz), 6.50 (1H, d, J=16.0 Hz), 4.84 (2H,s), 4.73 (1H, s), 4.68 (1H, s), 4.20 (2H, s), 1.74 (3H, s).

EXAMPLE 18(109)4-[2-[N-(Prop-2-enyl)-2-furanylsulfonylamino]-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.21 (hexane:AcOEt=1:1); NMR: δ 8.14-8.13 (2H, m), 7.45 (2H, d,J=8.5 Hz), 7.28 (1H, m), 7.10 (1H, d, J=7.5 Hz), 6.85 (1H, m), 6.84-6.76(1H, m), 6.71 (1H, s), 6.34 (1H, m), 5.88-5.79 (1H, m), 5.11-5.02 (4H,m), 4.33 (2H, bs), 2.32 (3H, bs).

EXAMPLE 18(110)4-[2-[N-(2-Methylprop-2-enyl)-2-furanylsulfonylamino]-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.24 (hexane:AcOEt=1:1); NMR: δ 8.14-8.13 (2H, m), 7.44 (2H, d,J=8 Hz), 7.26 (1H, m), 7.13 (1H, d, J=8 Hz), 6.82 (1H, m), 6.78-6.69(1H, m), 6.69 (1H, s), 6.33 (1H, m), 5.00 (2H, s), 4.76 (1H, dd, J=9.5,1.5 Hz), 4.30 (2H, bs), 2.32 (3H, s), 1.78 (3H, s).

EXAMPLE 18(111)4-[2-(N-Isobutyl-phenylsulfonylamino)-4-methylphenoxymethyl]cinnamicAcid

TLC: Rf 0.37 (CHCl₃:MeOH=9:1); NMR: δ 7.79 (1H, d, J=16.0 Hz), 7.70-7.60(2H, m), 7.50 (2H, d, J=8.0 Hz), 7.40-7.35 (1H, m), 7.30-7.20 (2H, m),7.20-7.10 (3H, m), 7.05 (1H, dd, J=2.0, 8.0 Hz,) 6.72 (1H, d, J=8.0 Hz),6.47 (1H, d, J=16.0 Hz), 4.9-4.5 (2H, m), 3.5-3.3 (2H, m), 2.29 (3H, s),1.7-1.6 (1H, m), 1.0-0.8 (6H, m).

EXAMPLE 18(112)4-[2-(N-Benzyl-methylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.62 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.64 (2H,d, J=8.4 Hz), 7.48 (2H, d, J=8.4 Hz), 7.24 (8H, m), 6.50 (1H, d, J=16.0Hz), 5.18 (2H, s), 4.77 (2H, s), 2.88 (3H, s).

EXAMPLE 18(113)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-4-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.26 (AcOEt:hexane=1:1); NMR: δ 8.11 (2H, d, J=8 Hz), 7.41 (2H,d, J=8 Hz), 7.25 (1H, m), 7.09 (1H, d, J=2 Hz), 7.06 (1H, dt, J=8,2 Hz),6.80 (1H, dd, J=4, 1 Hz), 6.76 (1H, d, J=8 Hz), 6.31 (1H, dd, J=2, 2Hz), 5.20-4.80 (2H, brs), 3.53 (2H, brs), 2.28 (3H, s), 1.67 (1H, m),0.92 (6H, brs).

EXAMPLE 18(114)4-[2-(N-Isopropyl-2-furanylsulfonylamino)-4-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.19 (AcOEt:hexane=1:1); NMR: δ 8.12 (2H, d, J=8 Hz), 7.55 (2H,d, J=8 Hz), 7.44 (1H, d, J=2 Hz), 7.11 (1H, dd, J=8, 2 Hz), 6.91 (1H,dd, J=3, 1 Hz), 6.87 (1H, d, J=3 Hz), 6.84 (1H, d, J=8 Hz), 6.42 (1H,dd, J=3, 1 Hz), 5.10 (2H, s), 4.48 (1H, m), 2.27 (3H, s), 1.12 (6H, d,J=7 Hz).

EXAMPLE 18(115)4-[2-[N-(2-Methylprop-2-enyl)-2-furanylsulfonylamino]-4-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.21 (AcOEt:hexane=1:1); NMR: δ 8.12 (2H, d, J=8 Hz), 7.42 (2H,d, J=8 Hz), 7.26 (1H, m), 7.07 (1H, d, J=2 Hz), 7.06 (1H, dd, J=8, 2Hz), 6.83 (1H, d, J=3 Hz), 6.75 (1H, d, J=8 Hz), 6.33 (1H, dd, J=3, 2Hz), 4.97 (2H, s), 4.77 (2H, s), 4.30 (2H, s), 2.28 (3H, s), 1.79 (3H,s).

EXAMPLE 18(116)4-[2-(N-Isopropyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]cinnamicAcid

TLC: Rf 0.20 (hexane:AcOEt=1:1); NMR: δ 7.80 (1H, d, J=16 Hz), 7.61-7.45(4H, m), 7.43 (1H, m), 6.93-6.88 (2H, m), 6.79-6.73 (2H, m), 6.47 (1H,d, J=16 Hz), 6.41 (1H, dd, J=3.5, 2 Hz), 5.07 (2H, s), 4.56-4.43 (1H,m), 2.34 (3H, s), 1.10 (6H, dd, J=6.5, 4 Hz).

EXAMPLE 18(117)4-[2-(N-Isopropyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.18 (hexane:AcOEt=1:1); NMR: δ 7.80 (1H, d, J=16 Hz), 7.63-7.51(4H, m), 7.46 (1H, dd, J=1.5, 1 Hz), 7.23-7.20 (3H, m), 6.94 (1H, dd,J=3.5, 1 Hz), 6.52-6.43 (3H, m), 5.14 (2H, s), 4.51-4.41 (1H, m), 1.09(6H, dd, J=6.5, 1 Hz).

EXAMPLE 18(118)4-[2-(N-Isopropyl-2-furanylsulfonylamino)-4-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.35 (AcOEt:hexane:AcOH=50:50:1); NMR: δ 8.16 (2H, d, J=8.5 Hz),7.60 (3H, m), 7.38 (1H, dd, J=1.0, 2.0 Hz), 7.26 (1H, m), 7.05 (1H, d,J=9.0 Hz), 6.95 (1H, d, J=3.0 Hz), 6.47 (1H, dd, J=2.0, 3.5 Hz), 5.22(2H, s), 4.52 (1H, sept, J=7.0 Hz), 1.12 (3H, d, J=7.0 Hz), 1.10 (3H, d,J=7.0 Hz).

EXAMPLE 18(119)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-4-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.35 (AcOEt:hexane:AcOH=50:50:1); NMR: δ 8.15 (2H, d, J=9.0 Hz),7.55 (1H, m), 7.48 (2H, d, J=9.0 Hz), 7.44 (1H, d, J=2.0 Hz), 7.35 (1H,dd, J=1.0, 2.0 Hz), 6.99 (1H, d, J=9.0 Hz), 6.86 (1H, dd, J=1.0, 2.0Hz), 6.39 (1H, dd, J=2.0, 4.0 Hz), 5.12 (2H, br), 3.52 (2H, d, J=7.0Hz), 1.64 (1H, m), 0.92 (6H, d, J=6.5 Hz).

EXAMPLE 18(120)4-[2-(N-Isopropyl-phenylsulfonylamino)-4-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.35 (AcOEt:hexane:AcOH=50:50:1); NMR: δ 7.81 (3H, m), 7.58-7.62(3H, m), 7.53 (1H, m), 7.49 (2H, d, J=8.0 Hz), 7.41 (2H, m), 7.24 (1H,d, J=2.0 Hz), 7.07 (1H, d, J=8.5 Hz), 6.49 (1H, d, J=16.5 Hz), 5.13 (1H,d, J=12.5 Hz), 5.12 (1H, d, J=12.5 Hz), 4.40 (1H, sept, J=6.5 Hz), 4.07(3H, d, J=6.5 Hz), 1.02 (3H, d, J=6.5 Hz).

EXAMPLE 18(121)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.36 (AcOEt:hexane:AcOH=50:50:1); NMR: δ 8.14 (2H, d, J=8.5 Hz),7.44 (2H, d, J=8.5 Hz), 7.26 (1H, m), 7.21 (1H, d, J=9.0 Hz), 6.98 (1H,dd, J=2.5, 8.0 Hz), 6.91 (1H, d, J=2.5 Hz), 6.82 (1H, d, J=4.5 Hz), 6.34(1H, d, J=2.0, 3.0 Hz), 5.00 (2H, br), 3.51 (2H, brs), 1.65 (1H, m),0.91 (6H, d, J=6.5 Hz).

EXAMPLE 18(122)4-[2-(N-Isopropyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]cinnamicAcid

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.2 Hz), 7.60 (2H,d, J=8.4 Hz), 7.50 (2H, d, J=8.4 Hz), 7.45-7.42 (1H, m), 7.02-6.90 (4H,m), 6.53-6.40 (2H, m), 5.07 (2H, s), 4.60-4.40 (1H, m), 1.10 (3H, d,J=6.6 Hz), 1.07 (3H, d, J=6.6 Hz).

EXAMPLE 18(123)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]cinnamicAcid

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=15.8 Hz), 7.58 (2H,d, J=8.0 Hz), 7.37 (2H, d, J=8.0 Hz), 7.25 (1H, dd, J=1.0, 1.8 Hz), 7.20(1H, d, J=8.2 Hz), 7.00-6.90 (2H, m), 6.81 (1H, dd, J=1.0, 3.6 Hz), 6.49(1H, d, J=15.8 Hz), 6.33 (1H, dd, J=1.8, 3.6 Hz), 4.95 (2H, s),3.60-3.40 (2H, m), 1.80-1.50 (1H, m), 0.90 (6H, d, J=6.6 Hz).

EXAMPLE 18(124)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.20 (hexane:AcOEt=1:1); NMR: δ 8.18-8.14 (2H, m), 7.48-7.40(2H, m), 7.30-7.26 (2H, m), 7.16 (1H, m), 6.84 (1H, dd, J=3.5, 1 Hz),6.35 (1H, dd, J=3.5, 2 Hz), 5.07 (2H, s), 3.54 (2H, d, J=7 Hz), 1.64(1H, sept., J=7 Hz), 0.90 (6H, d, J=7 Hz).

EXAMPLE 18(125)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-4-chlorophenoxymethyl]benzoicAcid

TLC: Rf 0.36 (CHCl₃:MeOH=9:1); NMR: δ 8.14 (2H, d, J=8.4 Hz), 7.44 (2H,d, J=8.4 Hz), 7.34-7.20 (3H, m), 6.90-6.80 (2H, m), 6.37 (1H, dd, J=1.8,3.0 Hz), 5.03 (2H, s), 3.51 (2H, d, J=7.2 Hz), 1.80-1.50 (1H, m), 0.91(6H, d, J=6.6 Hz).

EXAMPLE 18(126)4-[2-(N-Isobutyl-2-furanylsulfonylamino)-4-methylphenoxymethyl]cinnamicAcid

TLC: Rf 0.33 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.57 (2H,d, J=8.0 Hz), 7.36 (2H, d, J=8.0 Hz), 7.28-7.22 (1H, m), 7.12-7.02 (2H,m), 6.84-6.74 (2H, m), 6.48 (1H, d, J=16.0 Hz), 6.32 (1H, dd, J=1.8, 3.6Hz), 4.92 (2H, s), 3.54 (2H, d, J=7.0 Hz), 2.28 (3H, s), 1.80-1.60 (1H,m), 0.92 (6H, d, J=6.6 Hz).

EXAMPLE 18(127)4-[2-(N-Isobutyl-4-ethoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.35 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.09 (2H, d, J=8.5 Hz),7.52 (2H, d, J=8.5 Hz), 7.46 (1H, d, J=8.5 Hz), 7.25-7.29 (3H, m), 7.13(1H, brd, J=1.5 Hz), 6.73 (2H, d, J=9.0 Hz), 4.92 (2H, br), 3.96 (2H, q,J=7.5 Hz), 3.40 (2H, brs), 1.59 (1H, m), 1.42 (3H, t, J=7.5Hz), 0.90(6H, brd, J=6.0 Hz).

EXAMPLE 18(128)4-[2-(N-Methylphenylsulfonylamino)-4-chlorophenoxymethyl]benzoic Acid

TLC: Rf 0.43 (CHCl₃:MeOH: H₂O=9:1: 0.1); NMR (DMSO-d₆): δ 7.88 (2H, d,J=8.6 Hz), 7.66-7.38 (6H, m), 7.25-7.11 (4H, m), 4.95 (2H, s), 3.15 (3H,s).

EXAMPLE 19 Methyl4-[2-(N-Cyclopentylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoate

To a solution of methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate (251mg; prepared in Example 15.), triphenylphosphine (142 mg) andcyclopentylmethanol (54 mg) in THF (2 ml), diethyl azodicarboxylate (89μl; abbreviated as DEAD.) was added at 0° C. The mixture was stirredovernight at room temperature. The reaction solution was purified onsilica gel chromatography (hexane:AcOEt=7:1) to give the title compound(333 mg) having the following physical data.

TLC: Rf 0.51 (hexane:AcOEt=3:1); NMR: δ 8.01 (2H, d, J=8.4 Hz),7.63-7.58 (2H, m), 7.48-7.25 (5H, m), 7.17 (2H, d, J=8.4 Hz), 7.09 (1H,d, J=1.4 Hz), 4.83 (2H, br), 3.95 (3H, s), 3.55 (2H, d-like), 1.92-1.09(9H, m).

EXAMPLE 204-[2-(N-Cyclopentylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

By using methyl4-[2-(N-cyclopentylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoate(prepared in Example 19.), the title compounds having the followingphysical data was obtained by the same procedure as Example 2.

TLC: Rf 0.40 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR: δ 8.09 (2H, d, J=8.2 Hz),7.65-7.61 (2H, m), 7.47-7.20 (7H, m), 7.1 1 (1 H, d, J=1.8 Hz), 4.89(2H, br), 3.59-3.51 (2H, m), 1.93-1.10 (9H, m).

EXAMPLE 20(1)-20(30)

By using the corresponding compounds, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 6→Reference Example 7→Example 7→Example 19→Example 2 orReference Example 8→Reference Example 9→Reference Example 10→Example9→Example 19→Example 2.

EXAMPLE 20(1)4-[2-(N-Cyclopropylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH:H₂O=9:1:0.1); NMR: δ 8.09 (2H, d, J=8.2 Hz),7.70-7.65 (2H, m), 7.54-7.22 (7H, m), 7.14 (1H, d, J=1.8 Hz), 4.93 (2H,s), 3.51 (2H, d, J=7.2 Hz), 0.96-0.81 (1H, m), 0.44-0.35 (2H, m),0.10-0.02 (2H, m).

EXAMPLE 20(2)4-[2-(N-t-Butylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.5 (CHCl₃:MeOH=9:1); NMR: δ 8.12 (2H, d, J=8.0 Hz), 7.6-7.4(4H, m), 7.4-7.2 (5H, m), 7.09 (1H, d, J=1.8 Hz), 5.02 (1H, d, J=1 2.4Hz), 4.72 (1H, d, J=12.4 Hz), 3.53 (2H, s), 0.86 (9H, s).

EXAMPLE 20(3)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-phenylaceticAcid

TLC: Rf 0.47 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.79 (2H, d, J=7.6 Hz),7.20-7.50 (10H, m), 5.01 (2H, s), 4.28 (1H, sept, J=6.6 Hz), 3.71 (2H,s), 1.08 (3H, d, J=6.6 Hz), 1.01 (3H, d, J=6.6 Hz).

EXAMPLE 20(4)4-[2-(N-Isopropyl-propylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.33 (CHCl₃:MeOH=20:1); NMR (CD₃Cl): δ 8.13 (2H, d, J=8.0 Hz),7.54 (2H, d, J=8.0 Hz), 7.30-7.46 (3H, m), 5.19 (2H, s), 4.32 (1H, sept,J=6.2 Hz), 2.96 (2H, m), 1.78 (2H, m), 1.27 (2H, d, J=6.4 Hz), 1.12 (2H,d, J=6.4 Hz), 0.85 (3H, t, J=7.4 Hz).

EXAMPLE 20(5)4-[2-(N-Isopropyl-pentylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=20:1); NMR (CD₃Cl): δ 8.17 (2H, d, J=8.4 Hz),7.59 (2H, d, J=8.4 Hz), 7.12-7.41 (3H, m), 5.18 (2H, 3), 4.32 (1H, sept,J=6.6 Hz), 2.97 (2H, m), 1.74 (2H, m), 1.02-1.35 (8H, m), 0.82 (3H, t,J=6.8 Hz).

EXAMPLE 20(6)4-[2-(N-Isopropyl-butylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=9:1); NMR: δ 8.17 (2H, d, J=8.2 Hz), 7.59 (2H,d, J=8.2 Hz), 7.40 (1H, d, J=7.8 Hz), 7.3-7.2 (2H, m), 5.18 (2H, s),4.4-4.2 (1H, m), 3.1-2.9 (2H, m), 1.8-1.6 (2H, m), 1.4-1.0 (8H, m), 0.92(3H, t, J=7.2 Hz).

EXAMPLE 20(7)4-[2-(N-Isopropyl-hexylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.44 (CHCl₃:MeOH=9:1); NMR: δ 8.18 (2H, d, J=8.0 Hz), 7.59 (2H,d, J=8.0 Hz), 7.40 (1H, d, J=8.0 Hz), 7.3-7.2 (2H, m), 5.18 (2H, s),4.4-4.2 (1H, m), 3.0-2.9 (2H, m), 1.8-1.6 (2H, m), 1.3-1.0 (12H, m),0.85 (3H, t, J=7.4 Hz).

EXAMPLE 20(8)4-[2-(N-Isopropyl-heptylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.48 (CHCl₃:MeOH=9:1); NMR: δ 8.18 (2H, d, J=8.0 Hz), 7.59 (2H,d, J=8.0 Hz), 7.40 (1H, d, J=8.0 Hz), 7.3-7.2 (2H, m), 5.18 (2H, s),4.4-4.2 (1H, m), 3.0-2.9 (2H, m), 1.9-1.6 (2H, m), 1.4-1.0 (14H, m),0.86 (3H, t, J=6.2 Hz).

EXAMPLE 20(9)4-[2-(N-Isopropyl-4-hydroxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.28 (CHCl₃:MeOH=9:1); NMR: δ 8.13 (2H, d, J=8.2 Hz), 7.66 (2H,d, J=9.2 Hz), 7.50 (2H, d, J=8.2 Hz), 7.3-7.2 (3H, m), 6.72 (2H, d,J=9.2 Hz), 5.10 (2H, s), 4.4-4.2 (1H, m), 3.0-1.5 (2H, br), 1.10 (3H, d,J=6.6 Hz), 1.03 (3H, d, J=6.6 Hz).

EXAMPLE 20(10)4-[2-(N-Isopropyl-butylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.41 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.6 Hz), 7.57 (2H,d, J=8.6 Hz), 7.15 (1H, d, J=8.4 Hz), 6.9-6.8 (2H, m), 5.13 (2H, s),4.4-4.2 (1H, m), 3.1-2.9 (2H, m), 2.36 (3H, s), 1.8-1.6 (2H, m), 1.3-1.2(5H, m), 1.10 (3H, d, J=6.6 Hz), 0.81 (3H, t, J=7.4 Hz).

EXAMPLE 20(11)4-[2-(N-Isopropyl-hexylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.4 Hz), 7.57 (2H,d, J=8.4 Hz), 7.15 (1H, d, J=8.4 Hz), 7.1-7.0 (2H, m), 5.13 (2H, s),4.4-4.2 (1H, m), 3.0-2.9 (2H, m), 2.36 (3H, s), 1.8-1.6 (2H, m), 1.3-1.0(12H, m), 0.84 (3H, t, J=6.4 Hz).

EXAMPLE 20(12)4-[2-(N-Isopropyl-heptylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.47 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.0 Hz), 7.57 (2H,d, J=8.0 Hz), 7.15 (1H, d, J=8.4 Hz), 6.9-6.8 (2H, m), 5.13 (2H, s),4.4-4.2 (1H, m), 3.0-2.9 (2H, m), 2.36 (3H, s), 1.9-1.6 (2H, m), 1.3-1.0(14H, m), 0.85 (3H, t, J=6.2 Hz).

EXAMPLE 20(13)4-[2-(N-Isopropyl-methylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.13 (hexane:AcOEt=1:1); NMR: δ 8.17-8.13 (2H, m), 7.58-7.53(2H, m), 7.17-7.12 (1H, m), 6.8 (2H, m), 5.1 (2H, m), 4.33 (1H, sept.,J=6.5 Hz), 2.90 (3H, s), 2.36 (3H, s), 1.26 (3H, d, J=6.5 Hz), 1.09 (3H,d, J=6.5 Hz).

EXAMPLE 20(14)4-[2-(N-Isopropyl-ethylsulfonylamino)-5-methylphenoxymethyl]benzoic Acid

TLC: Rf 0.20 (hexane:AcOEt=1:1); NMR: δ 8.17-8.13 (2H, m), 7.59-7.55(2H, m), 7.17-7.13 (1H, m), 6.8 (2H, m), 5.1 (2H, m), 4.33 (1H, sept.,J=7 Hz), 3.01 (2H, q, J=7 Hz), 2.36 (3H, s), 1.29-1.20 (6H, m), 1.09(3H, d, J=6.5 Hz).

EXAMPLE 20(15)4-[2-(N-Isopropyl-2-phenylethylsulfonylamino)-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.24 (hexane:AcOEt=1:1); NMR: δ 8.00-7.96 (2H, m), 7.44-7.40(2H, m), 7.26-7.14 (4H, m), 7.05-7.01 (2H, m), 6.85-6.81 (2H, m), 5.07(2H, s), 4.42-4.27 (1H, m), 3.4-3.2 (2H, m), 3.2-3.0 (2H, m), 2.36 (3H,s), 1.25 (3H, d, J=6.5 Hz), 1.09 (3H, d, J=6.5 Hz).

EXAMPLE 20(16)4-[2-(N-Isopropyl-benzylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.22 (hexane:AcOEt=1:1); NMR: δ 8.15-8.11 (2H, m), 7.63-7.59(2H, m), 7.3 (2H, m), 6.92-6.88 (1H, m), 6.81-6.70 (2H, m), 5.2 (2H, m),4.29 (2H, s), 4.18-4.02 (1H, m), 2.35 (3H, s), 1.12 (3H, d, J=6.5 Hz),1.04 (3H, d, J=6.5 Hz).

EXAMPLE 20(17)4-[2-(N-t-Butylmethylphenylsulfonylamino)-4-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.37 (CHCl₃:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8 Hz), 7.55 (2H,m), 7.39 (1H, m), 7.32-7.20 (4H, m), 7.17 (1H, d, J=2 Hz), 7.03 (1H, dd,J=8 and 2 Hz), 6.68 (1H, d, J=8 Hz), 4.90 (1H, d, J=13 Hz), 4.59 (1H, d,J=l 3 Hz), 3.57 (1H, d, J=14 Hz), 3.50 (1H, d, J=14 Hz), 2.28 (3H, s),0.88 (9H, s).

EXAMPLE 20(18)4-[2-(N-Isopropyl-methylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.32 (CHCl₃:MeOH=9:1); NMR: δ 8.17 (2H, d, J=8.5 Hz), 7.58 (2H,d, J=8.5 Hz), , 7.43-7.23 (3H, m), 5.20 (2H, s), 4.32 (1H, m), 2.91 (3H,s), 1.29 (3H, d, J=7 Hz), 1.10 (3H, d, J=7 Hz).

EXAMPLE 20(19)4-[2-(N-Isopropyl-ethylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.36 (CHCl₃:MeOH=9:1); NMR: δ 8.18 (2H, d, J=8.5 Hz), 7.59 (2H,d, J=8.5 Hz), 7.43-7.23 (3H, m), 5.19 (2H, s), 4.33 (1H, m), 3.03 (2H,q, J=7.5 Hz), 1.32-1.17 (6H, m), 1.09 (3H, d), J=7 Hz).

EXAMPLE 20(20)4-[2-(N-Isopropyl-cyclopentylmethylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.26 (hexane:AcOEt=1:1); NMR: δ 8.17-8.13 (2H, m), 7.59-7.55(2H, m), 7.16-7.12 (1H, m), 6.83-6.80 (2H, m), 5.13 (2H, s), 4.31 (1H,sept., J=7 Hz), 3.04-3.00 (2H, m), 2.36 (3H, s), 2.4-2.2 (1H, m),2.0-1.8 (2H, m), 1.6-1.4 (4H, m), 1.24 (3H, d, J=7 Hz), 1.3-1.1 (2H, m),1.09 (3H, d, J=7 Hz).

EXAMPLE 20(21)4-[2-(N-Cyclohexylmethyl-propylsulfonylamino)-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH=9:1); NMR: δ 8.16 (2H, d, J=8.6 Hz), 7.54 (2H,d, J=8.6 Hz), 7.26 (1H, d, J=8.6 Hz), 6.9-6.8 (2H, m), 5.17 (2H, s),3.5-3.4 (2H, m), 2.9-2.8 (2H, m), 2.35 (3H, s), 2.0-1.0 (13H, m), 0.84(3H, t, J=8.0 Hz), 4.0-1.0 (1H, br).

EXAMPLE 20(22)4-[2-(N-Cyclopentylmethyl-propylsulfonylamino)-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.38 (CHCl₃:MeOH=9:1); NMR: δ 8.16 (2H, d, J=8.4 Hz), 7.54 (2H,d, J=8.4 Hz), 7.26 (1H, d, J=8.4 Hz), 6.9-6.8 (2H, m), 5.17 (2H, s),3.6-3.5 (2H, m), 2.9-2.8 (2H, m), 2.35 (3H, s), 2.0-1.0 (11H, m), 0.84(3H, t, J=7.6 Hz), 6.0-4.0 (1H, br).

EXAMPLE 20(23)4-[2-(N-Isopropyl-propylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.32 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.80 (1H, d, J=16.2 Hz),7.61 (2H, d, J=8.6 Hz), 7.51 (2H, d, J=8.6 Hz), 7.39 (1H, d, J=8.8 Hz),7.24-7.33 (2H, m), 6.49 (1H, d, J=16.2 Hz), 5.12 (2H, s), 4.31 (1H, m),2.95 (2H, m), 1.77 (2H, m), 1.26 (3H, d, J=6.6 Hz), 1.09 (3H, d, J=6.6Hz), 0.82 (3H, t, J=7.2 Hz).

EXAMPLE 20(24)4-[2-(N-Isopropyl-pentylsulfonylamino)-5-trifluoromethylphenoxymethyl]-cinnamicAcid

TLC: Rf 0.27 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.80 (1H, d, J=1 6.0 Hz),7.61 (2H, d, J=8.4 Hz), 7.51 (2H, d, J=8.4 Hz), 7.39 (1H, m), 7.24-7.33(2H, m), 6.48 (1H, d, J=16.0 Hz), 5.12 (2H, s), 4.31 (1H, sept, J=6.6Hz), 2.96 (2H, m), 1.72 (2H, m), 1.26 (3H, d, J=6.6 Hz), 1.05-1.23 (7H,m), 0.83 (3H, t, J=6.2 Hz).

EXAMPLE 20(25)4-[2-(N-Isopropyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.22 (hexane:AcOEt=1:1); NMR: δ 8.15 (2H, d, J=8 Hz), 7.59 (2H,d, J=8 Hz), 7.46 (1H, dd, J=2, 1 Hz), 7.23 (3H, m), 6.94 (1H, dd, J=3.5,1 Hz), 6.44 (1H, dd, J=3.5, 2 Hz), 5.18 (2H, s), 4.49 (1H, m), 1.10 (6H,dd, J=7, 2.5 Hz).

EXAMPLE 20(26)4-[2-(N-Isopropyl-2-thienylsulfonylamino)-5-trifluoromethylphenoxymethyl]-benzoicAcid

TLC: Rf 0.24 (hexane:AcOEt=1:1); NMR: δ 8.15 (2H, d, J=8.5 Hz), 7.57(2H, d, J=8.5 Hz), 7.54-7.51 (2H, m), 7.25 (3H, m), 7.01-6.99 (1H, m),5.19 (2H, s), 4.49-4.44 (1H, m), 1.10 (6H, d, J=6.5 Hz).

EXAMPLE 20(27)4-[2-(N-Isopropyl-4-chlorophenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH=10:1); NMR (DMSO-d₆): δ 7.93 (2H, d, J=8.4 Hz),7.73 (2H, d, J=8.4 Hz), 7.56 (1H, s), 7.50-7.28 (6H, m), 5.22 (2H, s),4.38 (1H, sept, J=6.6 Hz), 1.00 (3H, d, J=6.6 Hz), 0.93 (3H, d, J=6.6Hz).

EXAMPLE 20(28)4-[2-(N-Isopropyl-4-ethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=10:1); NMR (DMSO-d₆): δ 7.94 (2H, d, J=8.4 Hz),7.66 (2H, d, J=8.4 Hz), 7.55 (1H, d, J=1 Hz), 7.49 (2H, d, J=8.4 Hz),7.39 (1H, dd, J=8.4 Hz, 1 Hz), 7.32 (1H, J=8.4 Hz), 7.23 (2H, d, J=8.4Hz), 5.25 (2H, s), 4.14 (1H, sept, J=6.6 Hz), 2.61 (2H, q, J=7.4 Hz),1.14 (3H, t, J=7.4 Hz), 1.00 (3H, d, J=6.6 Hz), 0.93 (3H, d, J=6.6 Hz).

EXAMPLE 20(29)4-[2-(N-Isopropyl-4-propylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.41 (CHCl₃:MeOH=10:1); NMR (DMSO-d₆): δ 7.94 (2H, d, J=8.4 Hz),7.65 (2H, d, J=8.4 Hz), 7.55 (1H, d, J=1 Hz), 7.50 (2H, d, J=8.4 Hz),7.39 (1H, dd, J=8.4 Hz, 1 Hz), 7.32 (1H, d, J=8.4 Hz), 7.20 (2H, d,J=8.4 Hz), 5.25 (2H, s), 4.13 (1H, sept, J=6.6 Hz), 2.55 (2H, t, J=7.4Hz), 1.54 (2H, tq, J=7.4 Hz, 7.4 Hz), 0.97 (3H, d, J=6.6 Hz), 0.90 (3H,d, J=6.6 Hz), 0.84 (3H, t, J=7.4 Hz).

EXAMPLE 20(30)4-[2-(N-Isopropyl-4-butylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.41 (CHCl₃:MeOH=10:1); NMR (DMSO-d₆): δ 7.94 (2H, d, J=8.4 Hz),7.65 (2H, d, J=8.4 Hz), 7.55 (1H, d, J=1 Hz), 7.49 (2H, d, J=8.4 Hz),7.38 (1H, dd, J=8.4 Hz, 1 Hz), 7.33 (1H, J=8.4 Hz), 7.20 (2H, d, J=8.4Hz), 5.24 (2H, s), 4.14 (1H, sept, J=6.6 Hz), 2.57 (2H, t, J=7.4 Hz),1.49 (2H, m), 1.25 (2H, m), 0.98 (3H, d, J=6.6 Hz), 0.89 (3H, d, J=6.6Hz), 0.87 (3H, t, J=7.4 Hz).

EXAMPLE 21-21(16)

By using 2-nitrophenol or the corresponding compounds, the titlecompounds having the following physical data were obtained by the sameprocedure as Reference Example 6→Reference Example 12→Reference Example2→Example 2.

EXAMPLE 21 4-(2-Phenylsulfonylaminophenoxymethyl)benzoic Acid

TLC: Rf 0.35 (AcOEt:hexane:AcOH=6:13:1); NMR (DMSO-d₆): δ 12.86 (1H,brs), 9.53 (1H, brs), 7.91 (2H, d, J=8.0 Hz), 7.66 (2H, d, J=8.0 Hz),7.52 (1H, t, J=7.0 Hz), 7.45-7.25 (5H, m), 7.08 (1 H, t, J=9.0 Hz),6.95-6.80 (2H, m), 4.91 (2H, s).

EXAMPLE 21(1) 4-[2-(4-Chlorophenylsulfonylamino)phenoxymethyl]benzoicAcid

TLC: Rf 0.39 (AcOEt:hexane:AcOH=6:13:1); NMR (DMSO-d₆): δ 12.85 (1H,brs), 9.68 (1H, brs), 7.93 (2H, d, J=8.5 Hz), 7.60 (2H, d, J=8.5 Hz),7.36 (4H, d, J=8.5 Hz), 7.35-7.25 (1H, m), 7.12 (1 H, dt, J=7.5, 2.0Hz), 6.96-6.85 (2H, m), 4.92 (2H, s).

EXAMPLE 21(2) 4-(2-Phenylsulfonylamino-4-fluorophenoxymethyl)benzoicAcid

TLC: Rf 0.37 (AcOEt:hexane:AcOH=6:13:1); NMR (DMSO-d₆): δ 12.95 (1H,brs), 9.90 (1H, brs), 7.90 (2H, d, J=8.5 Hz), 7.72 (2H, d, J=7.0 Hz),7.58 (1H, m), 7.46 (2H, t, J=7.5 Hz), 7.37 (2H, d, J=8.5 Hz), 7.10 (1H,d, J=9.5 Hz), 6.92 (2H, d, J=7.0 Hz), 4.95 (2H, s).

EXAMPLE 21(3) 4-(2-Phenylsulfonylamino-5-fluorophenoxymethyl)benzoicAcid

TLC: Rf 0.42(AcOEt:hexane:AcOH=6:13:1); NMR (DMSO-d₆): δ 12.95 (1H,brs), 9.65 (1H, brs), 7.91 (2H, d, J=8.5 Hz), 7.60 (2H, d, J=7.0 Hz),7.52 (1H, t, J=7.0 Hz), 7.39 (2H, d, J=7.5 Hz), 7.35 (2H, d, J=7.5 Hz),7.26 (1H, dd, J=7.0,6.5 Hz), 6.84 (1H, dd, J=1 1.0, 2.5 Hz), 6.75 (1H,dt, J=8.5, 2.5 Hz), 4.90 (2H, s).

EXAMPLE 21(4) 4-(2-Phenylsulfonylamino-4-bromophenoxymethyl)benzoic Acid

TLC: Rf 0.25 (AcOEt:hexane:AcOH=6:13:1); NMR (DMSO-d₆): δ 12.97 (1H,brs), 9.97 (1H, brs), 7.90 (2H, d, J=8.0 Hz), 7.69 (2H, dd, J=7.5, 2Hz), 7.58 (1H, tt, J=7.5, 2Hz), 7.46 (2H, d, J=7.5Hz), 7.39 (1H, d,J=2.5 Hz), 7.36 (2H, d, J=8.0 Hz), 7.27 (1H, dd, J=9.0, 2.5 Hz), 6.89(1H, d, J=9 Hz), 4.97 (2H, s).

EXAMPLE 21(5) 4-(2-Phenylsulfonylamino-5-chlorophenylthiomethyl)benzoicAcid

TLC: Rf 0.50 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.99 (2H, d, J=8.4 Hz),7.78 (2H, m), 7.41-7.62 (5H, m), 7.23 (1H, dd, J=2.6, 8.8 Hz), 7.08 (1H,d, J=2.6 Hz), 7.05 (2H, d, J=8.6 Hz), 3.71 (2H, s).

EXAMPLE 21(6) 4-(2-Phenylsulfonylamino-4-methoxyphenoxymethyl)benzoicAcid

TLC: Rf 0.38 (CHCl₃:MeOH=17:3); NMR (DMSO-d₆): δ 7.90 (2H, d, J=8.5 Hz),7.71 (2H, d, J=8.0 Hz), 7.64-7.35 (5H, m), 6.90-6.80 (2H, m), 6.44 (1H,dd, J=9.0 and 3.0 Hz), 4.89 (2H, s), 3.65 (3H, m).

EXAMPLE 21(7)4-(2-Phenylsulfonylamino-4-trifluoromethylphenoxymethyl)benzoic Acid

TLC: Rf 0.32 (CHCl₃:MeOH=17:3); NMR (DMSO-d₆): δ 7.92 (2H, d, J=8.5 Hz),7.69 (2H, d, J=8.0 Hz), 7.63-7.34 (7H, m), 7.11 (1H, d, J=8.5 Hz), 5.09(2H, s).

EXAMPLE 21(8) 4-(2-Phenylsulfonylamino-4-methylphenoxymethyl)benzoicAcid

TLC: Rf 0.43 (AcOEt:hexane:AcOH=7:12:1); NMR (DMSO-d₆): δ 7.89 (2H, d,J=8.0 Hz), 7.66 (2H, d, J=7.0 Hz), 7.60-7.48 (1H, m), 7.41 (2H, d, J=8.0Hz), 7.35 (2H, d, J=8 Hz), 7.11 (1H, d, J=2.0 Hz), 6.90 (1H, dd, J=8.0,2.0 Hz), 6.76 (1H, d, J=8 Hz), 4.88 (2H, s), 2.19 (3H, s).

EXAMPLE 21(9) 4-(2-Phenylsulfonylamino-5-methylphenoxymethyl)benzoicAcid

TLC: Rf 0.43 (AcOEt:hexane:AcOH=7:12:1); NMR (DMSO-d₆): δ 7.91 (2H, d,J=8.5 Hz), 7.62 (2H, d, J=7.0 Hz), 7.57-7.45 (1H, m), 7.44-7.30 (4H, m),7.14 (1H, d, J=8.0 Hz), 6.75 (1H, s), 6.71 (1H, d, J=8.0 Hz), 4.88 (2H,s), 2.21 (3H, s).

EXAMPLE 21(10) 4-(2-Benzylsulfonylamino-5-chlorophenoxymethyl)benzoicAcid

TLC: Rf 0.52 (CHCl₃:MeOH:AcOH=100:5:1); NMR (DMSO-d₆): δ 7.96 (2H, d,J=8.0 Hz), 7.67 (2H, d, J=8.0 Hz), 7.29 (5H, s), 7.21 (1H, d, J=8.2 Hz),7.20 (1H, d, J=2.4 Hz), 6.95 (1H, dd, J=2.4, 8.2 Hz), 5.31 (2H, s), 4.38(2H, s).

EXAMPLE 21(11) 4-(2-Phenylsulfonylamino-5-methoxyphenoxymethyl)benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=4:1); NMR (DMSO-d₆): δ 7.90 (2H, d, J=8.5 Hz),7.59 (2H, d, J=8 Hz), 7.51 (1H, t, J=8 Hz), 7.44-7.28 (4H, m), 7.15 (1H,d, J=8.5 Hz), 6.54-6.47 (2H, m), 4.86 (2H, s), 3.69 (3H, s).

EXAMPLE 21(12) 3-(2-Phenylsulfonylamino-5-chlorophenoxymethyl)benzoicAcid

TLC: Rf 0.48 (AcOEt:hexane:AcOH=7:12:1); NMR (DMSO-d₆): δ 13.03 (1H,brs), 9.80 (1H, brs), 7.98 (1H, s), 7.95-7.86 (1H, m), 7.66 (2H, d,J=7.0 Hz), 7.58-7.46 (3H, m), 7.40 (2H, t, J=7.0 Hz), 7.27 (1H, d, J=8.5Hz), 7.07 (1H, d, J=2.5 Hz), 6.96 (1H, dd, J=8.5, 2.5 Hz), 4.96 (2H, s)

EXAMPLE 21(13)4-(2-Phenylsulfonylamino-4-chloro-5-methylphenoxymethyl)benzoic Acid

TLC: Rf 0.44 (CHCl₃:MeOH=4:1); NMR (DMSO-d₆): δ 7.91 (2H, d, J=8 Hz),7.66 (2H, d, J=7 Hz), 7.55 (1H, t, J=7.5 Hz), 7.47-7.30 (4H, m), 7.25(1H, s), 6.98 (1H, s), 4.93 (2H, s), 2.23 (3H, s).

EXAMPLE 21(14)4-(2-Phenylsulfonylamino-4,5-dichlorophenoxymethyl)benzoic Acid

TLC: Rf 0.42 (CHCl₃:MeOH4:1); NMR (DMSO-d₆): δ 7.92 (2H, d, J=8 Hz),7.69 (2H, d, J=7.5 Hz), 7.58 (1H, t, J=7.5 Hz), 7.50-7.31 (5H, m), 7.26(1H, s), 5.01 (2H, s).

EXAMPLE 21(15) 4-(2-Phenylsulfonylamino-5-chlorophenoxymethyl)phthalicAcid

TLC: Rf 0.36 (CHCl₃:MeOH:AcOH=15:4:1); NMR (DMSO-d₆): δ 6 13.23 (2H,brs), 9.86 (1H, s), 7.74-7.58 (4H, m), 7.56-7.30 (4H, m), 7.29 (1H, d,J=8.5 Hz), 7.06 (1H, d, J=2.0 Hz), 6.98 (1H, dd, J=8.5, 2 Hz), 4.94 (2H,s).

EXAMPLE 21(16) 4-(2-Phenylsulfonylamino-5-chlorophenoxy)benzoic Acid

TLC: Rf 0.46 (CHCl₃:MeOH=9:1); NMR: δ 7.99 (2H, d, J=9.0 Hz), 7.8-7.7(3H, m), 7.6-7.5 (1H, m), 7.5-7.3 (2H, m), 7.15 (1H, dd, J=2.2, 8.8 Hz),6.97 (1H, s), 6.77 (1H, d, J=2.2 Hz), 6.65 (2H, d, J=9.0 Hz).

REFERENCE EXAMPLE 18 Methyl4-[3-(2-nitro-5-chlorophenoxy)propyl]benzoate

(a) OH having compound

To a solution of methyl 4-(2-methoxycarbonylethyl)benzoate (1.0 g) inmixture of THF-MeOH (12 ml; THF:MeOH=5:1), sodium boron hydride (85 mg)was added. The mixture was stirred for 19 hours at room temperature. Tothe reaction mixture, ammonium chloride was added. After an excess ofreagent was decomposed, the mixture was extracted with ethyl acetate.The organic layer was washed, dried over and concentrated under thereduced pressure. The residue was purified on silica gel columnchromatography (AcOEt:hexane=2:3) to give the OH having compound (692mg) having the following physical data.

TLC: Rf 0.38 (hexane:AcOEt=1:1).

(b) title compound

To a solution of 2-nitro-5-chlorophenol (150 mg) in THF (2.0 ml), the OHhaving compound prepared in the above (a) (168 mg) andtriphenylphosphine (227 mg) were added in a stream of argon. After then,DEAD (136 μl) was added dropwise thereto at 0° C. The reaction mixturewas stirred for 24 hours at room temperature. After stirring, themixture was quenched by adding iced water and extracted with ethylacetate. After stirring, the mixture was quenched by adding iced waterand extracted with ethyl acetate. The organic layer was washed, driedover and concentrated under the reduced pressure. The residue waspurified on silica gel column chromatography (hexane:AcOEt=10:1→5:1) togive the title compound (309 mg) having the following physical data.

TLC: Rf 0.24 (hexane:AcOEt=5:1).

EXAMPLE 22 4-[3-(2-Phenylsulfonylamino-5-chlorophenoxy)propyl]benzoicAcid

By using methyl 4-[3-(2-nitro-5-chlorophenoxy)propyl]benzoate (preparedin Reference Example 18.), the title compound having the followingphysical data was obtained by the same procedure as Reference Example12→Reference Example 2→Example 2.

TLC: Rf 0.41 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.04 (2H, d, J=8.4 Hz),7.73 (2H, m), 7.50 (2H, m), 7.40 (2H, m), 7.21 (2H, d, J=8.2 Hz), 5.92(1H, brs), 6.91 (1H, dd, J=2.2, 8.6 Hz), 6.67 (1H, d, J=2.2 Hz), 3.75(2H, t, J=6.2 Hz), 2.70 (2H, t, J=7.0 Hz), 1.98 (2H, m).

EXAMPLE 22(1)-22(4)

By using corresponding diester, halfester or 4-acetylbenzoic Acid, thetitle compounds having the following physical data were obtained by thesame procedure as Reference Example 18→Reference Example 12→ReferenceExample 2→Example 2.

EXAMPLE 22(1)trans-4-(2-Phenylsulfonylamino-5-chlorophenoxymethyl)cyclohexanoic Acid

TLC: Rf 0.39 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.70 (2H, m), 7.36-7.59(4H, m), 6.92 (1H, brs), 6.91 (1H, dd, J=2.2, 8.4 Hz), 6.70 (1H, d,J=2.2 Hz), 3.55 (2H, d, J=6.2 Hz), 2.31 (1H, tt, J=3.8, 12.0 Hz),2.00-2.19 (2H, m), 1.35-1.85 (5H, m), 0.95 (2H, m).

EXAMPLE 22(2)cis-4-(2-Phenylsulfonylamino-5-chlorophenoxymethyl)cyclohexanoic Acid

TLC: Rf 0.53 (CHCl₃:MeOH AcOH=100:5:1); NMR: δ 7.70 (2H, m), 7.35-7.57(4H, m), 6.89 (1H, dd, J=2.2, 8.6 Hz), 6.84 (1H, brs), 6.69 (1H, d,J=2.2 Hz), 3.58 (2H, d, J=6.4 Hz), 2.70 (1H, m), 1.98-2.15 (2H, m),1.43-1.80 (5H, m), 1.15-1.40 (2H, m).

EXAMPLE 22(3) 6-(2-Phenylsulfonylamino-5-chlorophenoxymethyl)nicotinicAcid

TLC: Rf 0.40 (CHCl₃:MeOH:AcOH=100:10:1); NMR (DMSO-d₆): δ 9.90 (1H,brs), 9.02 (1H, d, J=1.6 Hz), 8.27 (1H, dd, J=2.2, 8.4 Hz), 7.62 (2H,m), 7.49 (2H, m), 7.31-7.39 (2H, m), 7.31 (1H, d, J=8.6 Hz), 7.08 (1H,d, J=2.2 Hz), 7.02 (1H, dd, J=2.2, 8.6 Hz), 4.96 (2H, s).

EXAMPLE 22(4) 4-[1RS-(2-Phenylsulfonylamino-5-chlorophenoxy)ethyl]benzoic Acid

TLC: Rf 0.48 (CHCl₃:MeOH=9:1); NMR: δ 12.0-10.0 (1H, br), 8.00 (2H, d,J=8.4 Hz), 7.78 (2H, d, J=7.8Hz), 7.7-7.4 (4H, m), 7.1-7.0 (3H, m), 6.88(1H, dd, J=2.2, 8.8Hz), 6.45 (1H, s), 5.14 (1H, q, J=6.4 Hz), 1.50 (3H,d, J=6.4 Hz).

REFERENCE EXAMPLE 19 2-nitro-5-Trifluoromethylphenyl Methoxymethyl Ether

To a solution of 2-nitro-5-trifluoromethylphenol (400 mg) in DMF (4.0ml), sodium hydride (77 mg) was added at 0° C. in a stream of argon. Themixture was stirred for 30 minutes After stirring, methoxymethylchloride (147 μl) was added dropwise thereto. The mixture was stirredfor 20 minutes. The reaction mixture was quenched by iced water andextracted with ethyl acetate. The layer containing ethyl acetate waswashed, dried over and concentrated under the reduced pressure. Theresidue was purified on silica gel column chromatography(hexane:AcOEt=20:1) to give the title compound (353 mg) having thefollowing physical data.

TLC: Rf 0.44 (hexane:AcOEt=10:1).

REFERENCE EXAMPLE 20 2-Amino-5-trifluoromethylphenyl Methoxymethyl Ether

To a solution of 2-nitro-5-trifluoromethylphenyl methoxymethyl ether(353 mg; prepared in Reference Example 19.) in MeOH (3.5 ml), 10% Pd—C(30 mg) was added in a stream of argon. The mixture was stirredvigorously at room temperature under hydrogen atmosphere. The reactionmixture was filtered through celite and concentrated under the reducedpressure to give the title compound (313 mg) having the followingphysical data.

TLC: Rf 0.44 (hexane:AcOEt=3:1).

REFERENCE EXAMPLE 21 MethylN-(2-Methoxymethoxy-4-trifluoromethylphenyl)-phenylsulfonylaminoacetate

By using 2-amino-5-trifluoromethylphenyl methoxymethyl ether (313 mg;prepared in Reference Example 20.), the title compound (625 mg) havingthe following physical data was obtained by the same procedure asReference Example 2→Example 17.

TLC: Rf 0.66 (benzene:acetone=9:1).

REFERENCE EXAMPLE 221,1-Dimethyl-2-[N-(2-methoxymethoxy-4-trifluoromethylphenyl)-phenylsulfonylamino]ethanol

To a solution of methylN-(2-methoxymethoxy-4-trifluoromethylphenyl)-phenylsulfonylaminoacetate(525 mg; prepared in Reference Example 21.) in THF (6.0 ml),methylmagnesium bromide (2.67 ml) was added dropwise in a stream ofargon at 0° C. The mixture was stirred for 30 minutes. The reactionmixture was quenched by iced water, extracted with ethyl acetate,washed, dried over and concentrated under the reduced pressure. Theresidue was purified on silica gel column chromatography(hexane:AcOEt=2:1) to give the title compound (380 mg) having thefollowing physical data.

TLC: Rf 0.26 (hexane:AcOEt=2:1).

REFERENCE EXAMPLE 231,1-Dimethyl-2-[N-(2-hydroxy-4-trifluoromethylphenyl)-phenylsulfonylamino]ethanol

To a solution of1,1-dimethyl-2-[N-(2-methoxymethoxy-4-trifluoromethylphenyl)-Phenylsulfonylamino]ethanol(380 mg; prepared in Reference Example 22.) in THF (4.0 ml), 6N HCl (0.8ml) was added. The mixture was stirred for 2 days at room temperature.The reaction mixture was diluted with ethyl acetate, washed, dried overand concentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (hexane:AcOEt=2:1) to give the titlecompound (291 mg) having the following physical data.

TLC: Rf 0.29 (benzene:acetone=9:1).

REFERENCE EXAMPLE 242-(N-Isopropyl-Phenylsulfonylamino)-5-trifluoromethylphenol

By using 2-amino-5-trifluoromethylphenyl methoxymethyl ether (preparedin Reference Example 20.), the title compound having the followingphysical data was obtained by the same procedure as Reference Example2→Example 17→Reference Example 23.

TLC: Rf 0.57 (hexane:AcOEt=5:2).

EXAMPLE 234-[2-[N-(2-Hydroxy-2-methylpropyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

By using1,1-dimethyl-2-[N-(2-hydroxy-4-trifluoromethylphenyl)-phenylsulfonylamino]ethanol(prepared in Reference Example 23.), the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 6→Example 2.

TLC: Rf 0.48 (CHCl₃:MeOH:AcOH=100:5:1); NMR (CD₃COCD₃): δ 8.03 (2H, brd,J=8.2 Hz), 7.47-7.66 (4H, m), 7.30-7.47 (6H, m), 5.21 (1H, m), 4.89 (1H,m), 3.79 (2H, s), 1.20 (6H, s).

EXAMPLE 23(1)-23(3)

By using2-[N-(2-hydroxy-2-methylpropyl)-phenylsulfonylamino]-5-trifluoromethylphenol(prepared in Reference Example 23.), the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 6→Example 2.

EXAMPLE 23(1)4-[2-[N-(2-Hydroxy-2-methylpropyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.53 (CHCl₃:MeOH=9:1); NMR: δ 7.80 (1H, d, J=16.0 Hz), 7.54 (6H,m), 7.35 (6H, m), 6.49 (1H, d, J=16.0 Hz), 4.99 (1H, m), 4.81 (1H, m),3.63 (2H, m), 1.21 (6H, s).

EXAMPLE 23(2)4-[2-[N-(2-Hydroxy-2-methylpropyl)-phenylsulfonylamino]-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.45 (CHCl₃:MeOH=9:1); NMR: δ 8.09 (2H, d, J=8.4 Hz), 7.60 (2H,m), 7.28-7.44 (5H, m), 7.06 (1H, m), 6.71 (2H, m), 5.00 (1H, d, J=1 2.8Hz), 4.74 (1H, d, J=1 2.8 Hz), 3.69 (1H, d, J=14.2 Hz), 3.57 (1H, d,J=14.2 Hz), 2.33 (3H, s), 2.13 (1H, s), 1.25 (3H, bs), 1.19 (3H, bs).

EXAMPLE 23(3)4-[2-[N-(2-Hydroxy-2-methylpropyl)-2-furanylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.42 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.4 Hz), 7.52 (2H,d, J=8.4 Hz), 7.21-7.34 (4H, m), 6.82 (1H, m), 6.38 (1H, m), 5.12 (2H,m), 3.76 (2H, m), 2.12 (1H, s), 1.23 (6H, bs).

EXAMPLE 244-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-phenoxyAcetic Acid

By using 2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenol(prepared in Reference Example 24.), the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 18 (b)→Example 2.

TLC: Rf 0.39 (AcOEt:hexane AcOH=9:10:1); NMR: δ 7.80 (2H, d, J=7.5 Hz),7.49 (1H. t, J=7.5 Hz), 7.40-7.20 (7H, m), 6.95 (2H, d, J=8.5 Hz), 4.98(2H, s), 4.72 (2H, s), 4.28 (1H, qn, J=6.5Hz), 1.06 (3H, d, J=6.5 Hz),1.01 (3H, d, J=6.5 Hz).

EXAMPLE 24(1)-24(10)

By using the corresponding compounds, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 18 (b)→Example 2.

EXAMPLE 24(1)5-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-thiophene-2-carboxylicAcid

TLC: Rf 0.54 (CHCl₃:MeOH:AcOH=90:9:1); NMR: δ 7.9-7.7 (3H, m), 7.6-7.3(3H, m), 7.3-7.2 (3H, m), 7.16 (1H, d, J=4.0 Hz), 5.20 (2H, s), 4.5-4.3(1H, m), 1.10 (3H, d, J=3.8Hz), 1.32 (3H, d, J=3.8 Hz).

EXAMPLE 24(2)5-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]furan-2-carboxylicAcid

TLC: Rf 0.17 (CHCl₃:MeOH 5:1); NMR: δ 7.76 (2H, d, J=8Hz), 7.54-7.29(3H, m), 7.29-7.13 (4H, m), 6.52 (1H, m), 5.00 (2H, s), 4.31 (1H, m),0.98 (6H, m).

EXAMPLE 24(3)4-[2-(N-Isopropyl-Phenylsulfonylamino)-5-methylphenoxymethyl]phenoxyaceticAcid

TLC: Rf 0.09 (AcOEt); NMR: δ 7.81 (2H, d, J=7.5 Hz), 7.50-7.30 (5H, m),7.00-6.91 (3H, m), 6.82-6.73 (2H, m), 4.91 (2H, s), 4.71 (2H, s), 4.27(1H, sept, J=7 Hz), 2.36 (3H, s), 1.05 (3H, d, J=7 Hz), 1.01 (3H, d, J=7Hz).

EXAMPLE 24(4)5-[2-(N-Isopropyl-phenylsulfonylamino)-5-methylphenoxymethyl]thiophene-2-carboxylicAcid

TLC: Rf 0.30 (CHCl₃:MeOH=9:1); NMR: δ 7.9-7.7 (3H, m), 7.5-7.4 (1H, m),7.4-7.3 (2H, m), 7.12 (1H, d, J=3.6 Hz), 7.01 (1H, d, J=8.2 Hz), 6.9-6.7(2H, m), 5.12 (2H, s), 4.5-4.3 (1H, m), 2.38 (3H, s), 1.51 (3H, d, J=2.4Hz), 1.05 (3H, d, J=2.4 Hz).

EXAMPLE 24(5)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-methylphenoxymethyl]cinnamicAcid

TLC: Rf 0.39 (hexane:AcOEt=1:2); NMR: δ 7.86-7.78 (3H, m), 7.60-7.26(7H, m), 6.97 (1H, d, J=8 Hz), 6.80-6.74 (2H, m), 6.48 (1H, d, J=16 Hz),5.01 (2H, s), 4.36 (1H, sept., J=6.5 Hz), 1.05 (6H, d, J=6.5 Hz).

EXAMPLE 24(6)4-[2-(N-isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]phenoxyaceticAcid

TLC: Rf 0.10 (CHCl₃:MeOH=10:1); NMR: δ 7.80-7.76 (2H, m), 7.52-7.44 (1H,m), 7.35-7.26 (4H, m), 7.05-6.91 (5H, m), 4.91 (2H, s), 4.72 (2H, s),4.28 (1H, sept., J=7 Hz), 1.05 (3H, d, J=7 Hz), (2H, d, J=7 Hz).

EXAMPLE 24(7)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]cinnamicAcid

TLC: Rf 0.31 (hexane AcOEt=1:1); NMR: δ 7.85-7.77 (2H, m), 7.60-7.35(7H, m), 7.05-6.90 (3H, m), 6.48 (1H, d, J=l6 Hz), 5.01 (2H, s), 4.36(1H, sept., J=6.5 Hz), 1.04 (6H, d, J=7 Hz).

EXAMPLE 24(8) 5-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]thiophene-2-carboxylic Acid

TLC: Rf 0.42 (CHCl₃:MeOH 9:1); NMR: δ 7.8-7.7 (3H, m), 7.5-7.3 (3H, m),7.2-6.9 (4H, m), 5.15 (1H, d, J=13.2Hz), 5.08 (1H, d, J=13.2Hz), 4.5-4.3(1H, m), 5.5-4.0 (1H, br), 1.08 (3H, d, J=2.6 Hz), 1.05 (3H, d, J=2.6Hz).

EXAMPLE 24(9)5-[2-(N-Isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]furan-2-carboxylicAcid

TLC: Rf 0.37 (CHCl₃:MeOH=9:1); NMR: δ 7.9-7.7 (2H, m), 7.6-7.4 (3H, m),7.31 (1H, d, J=3.4 Hz), 7.0-6.9 (3H, m), 6.63 (1H, d, J=3.4 Hz), 5.03(1H, d, J=13.2 Hz), 4.96 (1H, d, J=13.2 Hz), 5.5-4.5 (1H, br), 4.4-4.2(1H, m), 1.03 (6H, d, J=6.6 Hz).

EXAMPLE 24(10)4-[2-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxy]-ethyl]benzoicAcid

TLC: Rf 0.40 (CHCl₃:MeOH=9:1); NMR: δ 8.07 (2H, d, J=8.5Hz), 7.83 (2H,d, J=7 Hz),7.65-7.45 (5H, m), 7.39 (2H, d, J=8.5 Hz), 7.25-7.08 (3H, m),4.37 (1H, m), 4.25-4.05 (2H, m), 3.08 (2H, d, J=7 Hz), 0.99 (3H, d,J=6.5 Hz), 0.84 (3H, d, J=6.5 Hz).

EXAMPLE 252-Methoxy-4-[2-(N-isopropyl-Phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

By using 2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenol(prepared in Reference Example 24.), the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 6→Example 2.

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 11.0-10.6 (1H, br), 8.21 (1H, d,J=-7.8 Hz), 7.9-7.8 (2H, m), 7.71 (1H, d, J=0.6 Hz), 7.7-7.4 (3H, m),7.3-7.2 (2H, m), 7.2-7.1 (1H, m), 7.00 (1H, d, J=7.8 Hz), 5.22 (2H, s),4.6-4.4 (1H, m), 4.18 (3H, s), 1.08 (3H, d, J=6.6 Hz), 0.92 (3H, d,J=6.6 Hz).

EXAMPLE 262hydroxy-4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

By using 2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenol(prepared in Reference Example 24.), the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 6→Reference Example 23→Example 2.

TLC: Rf 0.56 (CHCl₃:MeOH:AcOH=90:9:1); NMR: δ 10.51 (1H, s), 7.95 (1H,d, J=8.0 Hz), 7.9-7.8 (2H, m), 7.6-7.4 (3H, m), 7.3-7.2 (3H, m), 7.1-7.0(2H, m), 5.05 (2H, s), 4.5-4.3 (1H, m), 1.09 J=5.0 Hz), 1.06 (3H, d,J=5.0 Hz).

EXAMPLE 26(1)-26(2)

By using the corresponding compounds, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 6→Reference Example 23→Example 2.

EXAMPLE 26(1)2-Hydroxy-4-[2-(N-isopropyl-phenylsulfonylamino)-5-methylphenoxymethyl]-benzoicAcid

TLC: Rf 0.20 (CHCl₃:MeOH=17:3); NMR: δ 10.50 (1H, s), 7.92 (1H, d, J=8.5Hz), 7.83 (2H, m), 7.54-7.32 (3H, m), 7.05-6.93 (3H, m), 6.81-6.72 (2H,m), 4.97 (2H, s), 4.42 (1H, m), 2.35 (3H, s), 1.13-0.98 (6H, m).

EXAMPLE 26(2)2-Hydroxy-4-[2-(N-isopropyl-phenylsulfonylamino)-5-chlorophenoxymethyl]-benzoicAcid

TLC: Rf 0.21 (CHCl₃:MeOH=9:1); NMR: δ 7.93 (1H, d, J=8.0 Hz), 7.9-7.7(2H, m), 7.6-7.3 (3H, m), 7.1-6.9 (5H, m), 4.97 (2H, s), 4.5-4.3 (1H,m), 3.0-2.0 (2H, br), 1.07 (3H, d, J=6.2 Hz), 1.04 (3H, d, J=6.2 Hz).

REFERENCE EXAMPLE 25 4-Phenylsulfonylamino-3-nitrobenzotrifluoride

To a solution of 4-amino-3-nitrobenzotrifluoride (3.09 g) in THF sodiumhydride (660 mg) was added. The mixture was stirred for 30 minutes atroom temperature. After stirring, benzenesulfonylchloride (3.18 g) wasadded thereto. The mixture was stirred for 2 hours at room temperature.In addition, sodium hydride (420 mg) was added thereto. The mixture wasstirred for 1 hour. The reaction mixture was acidified by adding anaqueous solution of ammonium chloride and extracted with ethyl acetate.The organic layer was washed, dried over, filtered and concentrated togive the title compound (4.86 g) having the following physical data.

TLC: Rf 0.31 (hexane:AcOEt=3:1).

REFERENCE EXAMPLE 26 4-Phenylsulfonylamino-3-aminobenzotrifluoride

By using 4-phenylsulfonylamino-3-nitrobenzotrifluoride (2.4 g; preparedin Reference Example 25.), the title compound (1.7 g) having thefollowing physical data was obtained by the same procedure as ReferenceExample 12.

TLC: Rf 0.17 (hexane:AcOEt=3:1).

EXAMPLE 27 Methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenylaminomethyl)-benzoate

To a solution of 4-phenylsulfonylamino-3-aminobenzotrifluoride (100 mg;prepared in Reference Example 26.) and terephthal aldehyde acid methylester (78 mg) in MeOH (2 ml), acetic Acid (1.5 ml) was added. Themixture was stirred for 2 hours at room temperature. After stirring, asolution of sodium cyanoborohydride (30 mg) in MeOH (2 ml) was added.The mixture was stirred for 2 hours at room temperature. The reactionsolution was extracted with H₂O-AcOEt, washed, dried over, filtered andconcentrated. The precipitate was washed with hexane to give the titlecompound (146 mg) having the following physical data.

TLC: Rf 0.27 (hexane:AcOEt=2:1); NMR: δ 8.02 (2H, m), 7.76 (2H, m),7.6-7.4 (5H, m), 6.74-6.70 (2H, m), 6.55-6.50 (1H, m), 6.02 (1H, bs),5.35 (1H, m), 4.40 (2H, m), 3.92 (3H, s).

EXAMPLE 284-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenylaminomethyl]-benzoicAcid

By using methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenylaminomethyl)benzoate(prepared in Example 27.), the title compound having the followingphysical data was obtained by the same procedure as Example 17→Example2.

TLC: Rf 0.45 (hexane:AcOEt=1:11); NMR: δ 8.10 (2H, d, J=8.5 Hz), 7.8-7.7(2H, m), 7.6-7.4 (5H, m), 6.8-6.7 (2H, m), 6.7-6.6 (1H, m), 5.34 (1H,m), 4.69 (1H, sept, J=7 Hz), 4.45 (2H, d, J=6 Hz), 1.15 (3H, d, J=7 Hz),1.01 (3H, d, J=7 Hz).

EXAMPLE 29 Methyl4-[N-methyl-[2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenyl]aminomethyl]benzoate

Methyl4-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenylaminomethyl]benzoate(200 mg) prepared by the same procedure as Example 17 by using methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenylaminomethyl)benzoate(prepared in Example 27.) was dissolved in DMF (5 ml). Sodium hydride(64 mg) and methyl iodide (200 μl) were added thereto. The mixture wasstirred for 24 hours at 60° C. The reaction mixture was extracted withH₂O-AcOEt, washed, dried over, filtered and concentrated under thereduced pressure. The residue was purified on silica gel columnchromatography (hexane:AcOEt=5:1) to give the title compound (105 mg)having the following physical data.

TLC: Rf 0.54 (CH₂Cl₂); NMR: δ 8.0 (2H, m), 7.9 (2H, m), 7.6-7.5 (3H, m),7.4 (2H, m), 7.4-7.2 (2H, m), 7.0 (1H, m), 4.6-4.3 (2H, m), 3.92 (3H,m), 2.72 (3H, s), 1.2 (3H, m), 0.8 (3H, m).

EXAMPLE 304-[N-Methyl-[2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenyl]-aminomethyl]benzoicAcid

By using methyl4-[N-methyl-[2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenyl]aminomethyl]benzoate(prepared in Example 29.), the title compound having the followingphysical data was obtained by the same procedure as Example 2.

TLC: Rf 0.45 (hexane:AcOEt=1:1); NMR: δ 8.09 (2H, d, J=8 Hz), 7.9 (2H,m), 7.7-7.4 (5H, m), 7.2 (2H, m), 7.0 (1H, m), 4.6-4.4 (3H, m), 2.75(3H, s), 1.26 (3H, d, J=7 Hz), 0.85 (3H, d, J=7 Hz).

REFERENCE EXAMPLE 27 Methyl2-t-Butoxycarbonylamino-5-trifluoromethylbenzoate

4-t-butoxycarbonylaminobenzotrifluoride (3.90 g) was dissolved in THF.At −50° C., t-butyl lithium (30 ml) was added dropwise thereto. Themixture was stirred for 3 hours with keeping at −50° C. Carbon dioxidegas was bubbled into this mixture under stirring (the temperatureincreased to about −30° C.). The solvent was distilled out. Theback-extractraction of the residue with 2N NaOH-ether mixture solutionwas carried out. The aqueous layer was acidified by adding 2N HCl,extracted with ether, washed and dried over. In addition, the layercontaining ether was washed, dried over, filtered and concentrated aftercombining the said layer containing ether to give the crude compound.Such crude compound was dissolved in ether. A solution of diazomethanein ether was added thereto until the reaction solution became yellow.The reaction solution was concentrated and purified on silica gel columnchromatography (hexane:AcOEt=20:1→10:1) to give the title compound (3.80g) having the following physical data.

TLC: Rf 0.70 (hexane:AcOEt=3:1).

REFERENCE EXAMPLE 28 Methyl 2-Amino-5-trifluoromethylbenzoate

To a solution of methyl2-t-butoxycarbonylamino-5-trifluoromethylbenzoate (3.80 g; prepared inReference Example 27.) in methylene chloride (30 ml), trifluoroaceticacid (6 ml) was added. The mixture was stirred for 8 hours at roomtemperature. The solvent was distilled off azeotropically with toluenethree times. To the reaction mixture, an aqueous sodiumhydrogencarbonate solution was added to neutralize. The mixture wasextracted with ethyl acetate, washed, dried, filtered and concentratedunder the reduced pressure. The residue was purified on silica gelcolumn chromatography (hexane:AcOEt 5:1) to give the title compound(2.35 g) having the following physical data.

TLC: Rf 0.20 (hexane:AcOEt=5:1).

EXAMPLE 314-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylbenzoylamino]benzoicAcid

By using methyl 2-amino-5-trifluoromethylbenzoate (prepared in ReferenceExample 28.), the title compound having the following physical data wasobtained by the same procedure as Reference Example 2→Reference Example3→Example 1→Example 2.

TLC: Rf 0.25 (hexane:AcOEt=1:2); NMR: δ 10.01 (1H, s), 8.18-8.14 (3H,m), 7.93 (8H, m), 6.64 (1 H, d, J=8 Hz), 4.67 (1H, sept., J=6.5 Hz),1.09 (3H, d, J=6.5 Hz), 0.86 (3H, d, J=6.5 Hz).

REFERENCE EXAMPLE 29 Methyl4-[2-[N-[1,3-bis(t-Butyldimethylsilyloxy)prop-2-yl]-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoate

(a) 1,3-diOTBs having compound (intermediate)

To a solution of glycerol (2 g) in DMF (1 5 ml), solution oft-butyldimethylsilylchloride (6.5 g) and imidazole (3.3 g) in DMF (8 ml)was added dropwise slowly at 0° C. The solution was stirred for 3 hoursat room temperature. The reaction mixture was poured into water,extracted with AcOEt-hexane (AcOEt:hexane=1:1) mixture solution andpurified on silica gel column chromatography to give the 1,3-diOTBshaving compound (5.8 g) having the following physical data.

TLC: Rf 0.5 (hexane:AcOEt=9:1).

(b) title compound

By using methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate (180mg; prepared in Example 15.) and the 1,3-diOTBS having compound preparedin the above (a) (247 mg), the title compound (200 mg) having thefollowing physical data was obtained by the same procedure as Example19.

TLC: Rf 0.28 (hexane:AcOEt=9:1).

EXAMPLE 32 Methyl4-[2-[N-(1,3-Dihydroxyprop-2-yl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoate

To a solution of methyl4-[2-[N-[1,3-bis(t-butyldimethylsilyloxy)prop-2-yl]-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoate(200 mg; prepared in Reference Example 29.) in THF (3 ml), a solution oftetrabutylanmonimu fluoride (0.57 ml) in THF (1M) was added. Thesolution was stirred for 3 hours at room temperature. To the reactioncompound, water was added. The mixture was extracted with ethyl acetate,washed, dried over and purified on silica gel column chromatography (110mg) having the following physical data.

TLC: Rf 0.50 (CH₂Cl₂:MeOH=9:1); NMR: δ 8.08 (2H, d, J=8.2 Hz), 7.78 (2H,d, J=7.2 Hz), 7.70-7.24 (8H, m), 5. 14 (1H, d, J=12.0 Hz), 5.06 (1H, d,J=12.0 Hz), 4.50-4.30 (1H, m), 3.93 (3H, s), 3.80-3.20 (4H, m), 2.72(1H, dd, J=3.6, 18.2 Hz).

EXAMPLE 334-[2-[N-(1,3-Dihydroxyprop-2-yl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

By using methyl4-[2-[N-(1,3-dihydroxyprop-2-yl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoate(prepared in Example 32.), the title compound having the followingphysical data was obtained by the same procedure as Example 2.

TLC: Rf 0.51 (AcOEt:AcOH=99:1); NMR: δ 8.13 (2H, d, J=8.4 Hz), 7.8-7.7(2H, m), 7.6-7.2 (8H, m), 5.17 (1H, d, J=11.4 Hz), 5.08 (1H, d, J=11.4Hz), 4.5-4.3 (1H, m), 3.6-3.5 (2H, m), 3.4-3.2 (2H, m).

EXAMPLE 344-[2-[N-(1,3-Dimethoxyprop-2-yl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

By using methyl4-[2-[N-(1,3-dihydroxyprop-2-yl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoate(prepared in Example 32.), the title compound having the followingphysical data was obtained by the same procedure as Reference Example19→Example 2.

TLC: Rf 0.57 (CHCl₃:MeOH=9:1); NMR: δ 8.18 (2H, d, J=8.2 Hz), 7.8-7.7(2H, m), 7.63 (2H, d, J=8.2 Hz), 7.6-7.4 (3H, m), 7.3-7.2 (3H, m),5.18(2H, s), 4.5-4.4 (1H, m), 3.7-3.6 (1H, m), 3.5-3.0 (3H, m), 3.09 (3H,s), 3.04 (3H, s).

REFERENCE EXAMPLE 302-(N-Isopropyl-methylsulfonylamino)-5-trifluoromethylphenylmethoxymethyl Ether

By using 2-amino-5-trifluoromethylphenyl methoxymethyl ether andmesylchloride, the title compound having the following physical data wasobtained by the same procedure as Reference Example 2→Example 17.

TLC: Rf 0.40 (hexane:AcOEt=2:1).

REFERENCE EXAMPLE 31

2-(N-Isopropyl-2-hydroxyhexylsulfonylamino)-5-trifluoromethylphenylmethoxymethyl Ether

To a solution of2-(N-isopropyl-methylsulfonylamino)-5-trifluoromethylphenylmethoxymethyl ether (135 mg; prepared in Reference Example 30.) in THF(3.0 ml), hexamethylphosphoramide (420 μl) was added in a stream ofargon. At −78° C., n-butyl lithium (742 μl) was added dropwise thereto.The mixture was stirred for 1.5 hours. To the mixture, a solution ofvaleraldehyde (102 mg) in THF (1.0 ml) was added dropwise. The mixturewas stirred for 30 minutes. To the reaction mixture, water was added.The mixture was extracted with ethyl acetate, washed, dried over andconcentrated with the reduced pressure. The residue was purified onsilica gel column chromatography (hexane:AcOEt=4:1) to give the titlecompound (69 mg) having the following physical data.

TLC: Rf 0.49 (hexane:AcOEt=2:1).

REFERENCE EXAMPLE 322-(N-Isopropyl-1-hexenylsulfonylamino)-5-trifluoromethylphenylmethoxymethyl Ether

To a solution of2-(N-isopropyl-2-hydroxyhexylsulfonylamino)-5-trifluoromethylphenylmethoxymethyl ether (160 mg; prepared in Reference Example 31.) inmethylene chloride (2.0 ml), triethylamine(104 μl) and mesylchloride(35μl) were added in a stream of argon at 0° C. The mixture was stirredfor 10 minutes. To the mixture, 1,5-diazabicyclo[5,4,0]undecene (134 μl)was added. The mixture was stirred for 2 hours at room temperature. Tothe reaction mixture, diluted HCl was added. The mixture was extractedwith ethyl acetate, washed, dried over and concentrated with the reducedpressure. The residue was purified on silica gel column chromatography(hexane:AcOEt=8:1) to give the title compound (140 mg) having thefollowing physical data.

TLC: Rf 0.37 (hexane:AcOEt=3:1).

EXAMPLE 354-[2-(N-Isopropyl-1-hexenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

By using 2-(N-isopropyl-1-hexenylsulfonylamino)-5-trifluoromethylphenylmethoxymethyl ether (prepared in Reference Example 32.), the titlecompound having the following physical data was obtained by the sameprocedure as Reference Example 23→Reference Example 6→Example 2.

TLC: Rf 0.44 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.19 (2H, d, J=8.2 Hz),7.62 (2H, d, J=8.2 Hz), 7.22-7.45 (3H, m), 6.68 (1H, td, J=7.0, 15.0Hz), 6.09 (1H, td, J=1.4, 15.0 Hz), 5.19 (2H, s), 4.15 (1H, m), 1.97(2H, m), 1.16-1.40 (7H, m), 1.03 (3H, d, J=6.8 Hz), 0.86 (3H, m).

REFERENCE EXAMPLE 33 Methyl4-(2-Cyclopentylsulfinylamino-5-trifluoromethylphenoxymethyl)benzoate

To a solution of methyl4-(2-amino-5-trifluoromethylphenoxymethyl)benzoate (300 mg) in methylenechloride (3.0 ml), pyridine (187 μml) and triphenylphosphine (315 mg)were added in a stream of argon. At 0° C., cyclopentylsulfonylchloride(202 mg) was added dropwise thereto. The mixture was stirred for 6 hoursat room temperature. To the reaction mixture, water was added. Themixture was extracted with ethyl acetate, washed, dried over andconcentrated with the reduced pressure. The residue was purified onsilica gel column chromatography (hexane:AcOEt=2:1→1:1) to give thetitle compound (309 mg) having the following physical data.

TLC: Rf 0.23 (hexane:AcOEt=2:1).

EXAMPLE 36 Methyl4-(2-Cyclopentylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate

To a solution of methyl4-(2-cyclopentylsulfinylamino-5-trifluoromethylphenoxymethyl)benzoate(305 mg; prepared in Reference Example 33.) in methylene chloride (4.0ml), meta-chloroperbenzoic acid (456 mg) was added at 0° C. The mixturewas stirred for 1 hour. The reaction mixture was diluted with ethylacetate, washed, dried over and concentrated under the reduced pressureto give the title compound (317 mg) having the following physical data.

TLC: Rf 0.56 (hexane:AcOEt=2:1); NMR: δ 8.11 (2H, d, J=8.6 Hz), 7.73(1H, brd, J=9.0 Hz), 7.47 (2H, d, J=8.6 Hz), 7.25 (1H, m), 7.15 (1H, d,J=1.4 Hz), 6.95 (1H, brs), 5.21 (2H, s), 3.95 (3H, s), 3.54 (1H, m),1.53-2.16 (8H, m).

EXAMPLE 374-[2-(N-Isopropyl-cyclopentylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

By using methyl4-(2-cyclopentylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate(prepared in Example 36.), the title compound having the followingphysical data was obtained by the same procedure as Example 17→Example2.

TLC: Rf 0.40 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.17 (2H, d, J=8.4 Hz),7.61 (2H, d, J=8.4 Hz), 7.38 (1H, d, J=8.0 Hz), 7.28 (2H, m), 5.17 (2H,s), 4.36 (1H, sept, J=6.6 Hz), 3.51 (1H, m), 1.84-2.10 (3H, m),1.61-1.84 (3H, m), 1.30-1.56 (2H, m), 1.24 (3H, d, J=6.6 Hz), 1.08 (3H,d, J=6.6 Hz).

EXAMPLE 37(1)-37(7)

By using the corresponding compounds, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 33→Example 36→Example 17→Example 2.

EXAMPLE 37(1)4-[2-(N-Isopropyl-cyclohexylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.27 (AcOEt:hexane=1:1); NMR: δ 8.17 (2H, d, J=8 Hz), 7.61 (2H,d, J=8 Hz), 7.42 (1H, d, J=8 Hz), 7.28 (1H, d, J=8 Hz), 7.26 (1H, s),5.19 (2H, s), 4.32 (1H, m), 2.88 (1H, m), 2.25-2.04 (2H, m), 1.92-1.35(5H, m), 1.30-0.60 (9H, m).

EXAMPLE 37(2)4-[2-(N-Isopropyl-cyclohexylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.37 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.15 (2H, d, J=8.6 Hz),7.59 (2H, d, J=8.6 Hz), 7.17 (1H, d, J=8.4 Hz), 6.82 (2H, m), 5.13 (2H,s), 4.32 (1H, m), 2.88 (1H, tt, J=3.2, 12.0 Hz), 2.35 (3H, s),2.15 (2H,m), 1.36-1.90 (5H, m), 1.23 (3H, d, J=6.6 Hz), 1.12 (3H, d, J=6.6 Hz),0.82 (1H, m).

EXAMPLE 37(3)4-[2-(N-Isopropyl-isopropylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.34 (CHCl₃:MeOH AcOH=100:5:1); NMR: δ 8.18 (2H, d, J=8.4 Hz),7.60 (2H, d, J=8.4 Hz), 7.42 (1H, d, J=8.0 Hz), 7.23-7.33 (2H, m), 5.17(2H, s), 4.32 (1H, sept, J=6.6 Hz), 3.17 (1H, sept, J=7.0 Hz), 1.32 (3H,d, J=7.0 Hz), 1.25 (3H, d, J=6.6 Hz), 1.19 (3H, d, J=7.0 Hz), 1.09 (3H,d, J=6.6 Hz).

EXAMPLE 37(4)4-[2-(N-Isopropyl-isopropylsulfonylamino)-5-methylphenoxymethyl]benzoicAcid

TLC: Rf 0.46 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.15 (2H, d, J=8.2 Hz),7.57 (2H, d, J=8.2 Hz), 7.16 (1H, d, J=8.4 Hz), 6.81 (2H, m), 5.11 (2H,s), 4.31 (1H, sept, J=6.6 Hz), 3.16 (1H, sept, J=6.8 Hz), 2.36 (3H, s),1.31 (3H, d, J=6.8 Hz), 1.23 (3H, d, J=6.6 Hz), 1.18 (3H, d, J=6.6 Hz),1.08 (3H, d, J=6.8 Hz).

EXAMPLE 37(5)4-[2-(N-Isopropyl-isopropylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.20 (AcOEt:hexane=1:1); NMR: δ 7.79 (1H, d, J=1 5 Hz), 7.61(2H, d, J=8 Hz), 7.50 (2H, d, J=8 Hz), 7.40 (1H, d, J=8 Hz), 7.34-7.20(2H, m), 6.48 (1H, d, J=15 Hz), 5.12 (2H, s), 4.31 (1H, m), 3.14 (1H,m), 1.31 (3H, d, J=7 Hz), 1.25 (3H, d, J=7 Hz), 1.15 (3H, d, J=7 Hz),1.07 (3H, d, J=7 Hz).

EXAMPLE 37(6)4-[2-(N-Isopropyl-cyclopentylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.24 (AcOEt:hexane=1:1); NMR: δ 7.80 (1H, d, J=1 5 Hz), 7.61(2H, d, J=8 Hz), 7.53 (2H, d, J=8 Hz), 7.38 (1H, d, J=8 Hz), 7.30-7.22(2H, m), 6.48 (1H, d, J=15 Hz), 5.13 (2H, s), 4.35 (1H, m), 3.49 (1H,m), 2.20-1.16 (11H, m), 1.07 (3H, d, J=7 Hz).

EXAMPLE 37(7)4-[2-(N-Isopropyl-cyclohexylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.27 (AcOEt:hexane=1:1); NMR: δ 7.80 (1H, d, J=l 5 Hz), 7.61(2H, d, J=8 Hz), 7.52 (2H, d, J=8 Hz), 7.41 (1H, d, J=8 Hz), 7.34-7.20(2H, m), 6.48 (1H, d, J=l5 Hz), 5.13 (2H, s), 4.32 (1H, m), 2.87 (1H,m), 2.21-2.00 (2H, m),1.90-1.34 (5H, m), 1.26 (3H, d, J=7 Hz), 1.18-0.60(6H, m).

REFERENCE EXAMPLE 34 Methyl4-(3-Nitro-5-trifluoromethylpyridine-2-yloxymethyl)benzoate

To a solution of 2-hydroxy-3-nitro-5-trifluoromethylpyridine (1.0 g) intoluene (10 ml), methyl 4-chloromethylbenzoate (1.32 g) and silver oxide(1.23 g) were added in a stream of argon. The mixture was refluxed for18 hours with heating. The reaction mixture was filtered. The filtratewas concentrated. The residue was recrystallized from ethyl acetate togive the title compound (982 mg) having the following physical data.

TLC: Rf 0.34 (hexane:AcOEt=3:1).

EXAMPLE 384-(3-Phenylsulfonylamino-5-trifluoromethylpyridine-2-yloxymethyl)benzoicAcid

By using methyl4-(3-nitro-5-trifluoromethylpyridine-2-yloxymethyl)benzoate (prepared inReference Example 34.), the title compound having the following physicaldata was obtained by the same procedure as Reference Example12→Reference Example 2→Example 2.

TLC: Rf 0.50 (CHCl₃:MeOH:AcOH=100:5:1); NMR (DMSO-d₆): δ 12.94 (1H, m),10.46 (1H, m), 8.33 (1H, m), 7.89 (2H, d, J=8.4 Hz), 7.85 (1H, d, J=2.2Hz), 7.73 (2H, m), 7.43-7.65 (3H, m), 7.36 (2H, d, J=8.4 Hz), 5.33 (2H,s).

REFERENCE EXAMPLE 354-[2-(N-Methoxymethoxycarbonylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid·Methoxymethyl Ester

4-[2-(N-carboxymethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicacid (446 mg) prepared by the same procedure as Example 17→Example 2 byusing methyl4-(2-phenylsulfonylamino-5-trifluoromethylphenoxymethyl)benzoate(prepared in Example 15.) was dissolved in DMF (5 μl). To the solution,methoxymethyl chloride (160 ml) and triethylamine(300μl) were addeddropwise. The mixture was stirred for 2 hours at room temperature. Waterwas added thereto. The mixture was extracted with ethyl acetate, washed,dried over, filtered and concentrated to give the title compound (476mg) having the following physical data.

TLC: Rf 0.20 (hexane:AcOEt=3:1).

REFERENCE EXAMPLE 364-[2-[N-(N,N-Dimethylaminocarbonylmethyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid·Methoxymethyl Ester

To a solution of4-[2-(N-methoxymethoxycarbonylmethylphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicacid·methoxymethyl ester (476 mg; prepared in Reference Example 35.) inTHF (2 ml), dimethylamine(0.8 ml) was added. The mixture was stirred for3 days at room temperature. The solvent was distilled off. The residuewas purified on silica gel column chromatography (hexane:AcOEt=2:1:1) togive the title compound (290 mg) having the following physical data.

TLC: Rf 0.26 (hexane:AcOEt=1:1).

EXAMPLE 394-[2-[N-(N,N-Dimethylaminocarbonylmethyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicAcid

By using4-[2-[N-(N,N-dimethylaminocarbonylmethyl)-phenylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicacid methoxymethyl ester (prepared in Reference Example 36.), the titlecompound having the following physical data was obtained by the sameprocedure as Reference Example 23.

TLC: Rf 0.24 (AcOEt); NMR: δ 8.10-8.06 (2H, m), 7.71-6.64 (3H, m),7.55-7.47 (1H, m), 7.42-7.10 (6H, m), 4.94 (2H, s), 4.56 (2H, s), 3.04(3H, s) 2.86 (3H, s).

REFERENCE EXAMPLE 37 Methyl 4-Phenylsulfonylamino-3-methoxybenzoate

By using 4-nitro-3-hydroxybenzoic acid, the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 6→Reference Example 12→Reference Example 2.

TLC: Rf 0.12 (hexane:AcOEt=3:1).

REFERENCE EXAMPLE 381-Methyl-1-(4-phenylsulfonylamino-3-methoxyphenyl)ethanol

To a suspension of methyl 4-phenylsulfonylamino-3-methoxybenzoate (3.2g; prepared in Reference Example 37.) in THF (50 ml), methyl lithium inether (38.8 ml) was added dropwise at −65° C. The mixture was slowlywarmed to 5° C. over a period of 3 hours under stirring. The reactionmixture was neutralized by adding diluted HCl and extracted with ethylacetate. The organic layer was washed, dried over and concentrated togive the title compound having the following physical data.

TLC: Rf 0.18 (hexane:AcOEt=1:1).

REFERENCE EXAMPLE 391-Methyl-1-[4-(N-acetyl-phenylsulfonylamino)-3-methoxyphenyl]ethanol

To a solution of1-methyl-1-(4-phenylsulfonylamino-3-methoxyphenyl)ethanol (2.65 g;prepared in Reference Example 38.) in methylene chloride (15 ml), aceticanhydride (3.05 ml) and triethylamine (4.60 ml) were added. The mixturewas stirred overnight at room temperature. The solvent was distilledoff. The residue was purified on silica gel column chromatography(hexane:AcOEt=3 4) to give the title compound (2.33 g) having thefollowing physical data.

TLC: Rf 0.19 (hexane:AcOEt=1:1).

REFERENCE EXAMPLE 40 2-(N-Acetyl-phenylsulfonylamino)-5-isopropylphenylMethyl Ether

To a solution of1-methyl-1-[4-(N-acetyl-phenylsulfonylamino)-3-methoxyphenyl]ethanol(2.50 g; prepared in Reference Example 39.) in methylene chloride (10ml), trifluoroacetic acid (10 ml) and triethylsilane (3.3 ml) were addedat 0° C. The mixture was stirred for 1 hour at room temperature. Thereaction mixture was added to saturated sodium hydrogencarbonatecarefully The mixture was extracted with ethyl acetate. The organiclayer was washed, dried over and concentrated. The residue was purifiedon silica gel column chromatography (hexane:AcOEt=3:1) to give the titlecompound (2.33 g) having the following physical data.

TLC: Rf 0.24 (hexane:AcOEt=1:1).

REFERENCE EXAMPLE 41 2-(N-acetyl-phenylsulfonylamino)-5-isopropylphenol

To a solution of 2-(N-acetyl-phenylsulfonylamino)-5-isopropylphenylmethyl ether (2.28 g; prepared in Reference Example 40.) in methylenechloride (15 ml), boron tribromide (1.36 ml) was added at 0° C. Themixture was stirred for 5 hours at 10° C. The reaction mixture waspoured into iced water, extracted with ethyl acetate. The organic layerwas washed, dried over and concentrated. The residue was purified onsilica gel column chromatography (benzene:AcOEt=23:2) and recrystallizedfrom AcOEt-hexane mixture solution to give the title compound (1.55 g)having the following physical data.

TLC: Rf 0.24 (benzene:AcOEt=9:1).

REFERENCE EXAMPLE 42 Methyl4-[2-(N-Acetyl-phenylsulfonylamino)-5-isopropylphenoxymethyl]benzoate

By using 2-(N-acetyl-phenylsulfonylamino)-5-isopropylphenol (1.50 g;prepared in Reference Example 41.), the title compound (2.22 g) havingthe following physical data was obtained by the same procedure asReference Example 6.

TLC: Rf 0.24 (hexane:AcOEt=7:3).

REFERENCE EXAMPLE 43 4-(Phenylsulfonylamino)-3-methoxybenzyl Alcohol

A solution of methyl 4-phenylsulfonylamino-3-methoxybenzoate (1.5 g;prepared in Reference Example 37.) in THF (90 ml) was cooled to −78° C.in a stream of argon. The solution of diisobutylaluminum hydride (1.0 M)in hexane (22 ml) was added dropwise thereto. The mixture was stirredfor 4 hours at −78° C. After the temperature increased to roomtemperature, the mixture was diluted with ether (100 ml). A saturatedaqueous sodium sulfate (1.5 ml) was added thereto slowly. The mixturewas stirred for 30 minutes, dried over, filtered and concentrated togive the title compound (1.5 g)

TLC: Rf 0.31 (AcOEt:hexane=2:1).

REFERENCE EXAMPLE 44 4-Phenylsulfonylamino-3-methoxybenzaldehyde

To a solution of 4-phenylsulfonylamino-3-methoxybenzyl alcohol (522 mg;prepared in Reference Example 43.) in methylene chloride (1 5 ml),manganese dioxide (3 g) was added in a stream of argon. The solution wasstirred for 1 hour at room temperature. After the termination ofreaction, the reaction mixture was filtered. The filtrate wasconcentrated to give the title compound (404 mg) having the followingphysical data.

TLC: Rf 0.57 (AcOEt:hexane=3:2).

REFERENCE EXAMPLE 45 1-(4-Phenylsulfonylamino-3-methoxyphenyl)ethanol

A solution of 4-phenylsulfonylamino-3-methoxybenzaldehyde (400 mg;prepared in Reference Example 44.) in THF (10 ml) was cooled to at −78°C. mg; prepared in Reference Example 44.) in THF (10 ml) was cooled toat −78° C. in a stream of argon. A solution of methyl lithium (1.0M) indiethyl ether (3.4 ml) was added dropwise thereto. The mixture wasstirred for 20 minutes. After the termination of reaction, a mixture ofH₂O+1N HCl was added thereto to stop the reaction. The mixture wasextracted with ethyl acetate three times. The organic layer was washed,dried over and purified on silica gel column chromatography(AcOEt:hexane=1:1) to give the title compound (421 mg) having thefollowing physical data.

TLC: Rf 0.34 (AcOEt:hexane=3:2).

EXAMPLE 40 4-(2-Phenylsulfonylamino-5-isopropylphenoxymethyl)benzoicAcid

By using methyl4-[2-(N-acetyl-phenylsulfonylamino)-5-isopropylphenoxymethyl]benzoate(2.00 g; prepared in Reference Example 42.), the title compound (1.66 g)having the following physical data was obtained by the same procedure asExample 2.

TLC: Rf 0.49 (CHCl₃:MeOH=4:1); NMR (DMSO-d₆): δ 7.84 (2H, d, J=8.5 Hz),7.79-7.53 (5H, m), 7.41 (2H, d, J=8.5 Hz), 6.90 (1H, d, J=8 Hz), 6.63(1H, d, J=2 Hz), 6.55 (1H, dd, J=8 and 2 Hz), 4.82 (2H, s), 2.72 (1H,m), 1.10 (6H, d, J=7 Hz).

EXAMPLE 41

By using 1-(4-phenylsulfonylamino-3-methoxyphenyl)ethanol (prepared inReference Example 45.), the title compound having the following physicaldata was obtained by the same procedure as Reference Example40→Reference Example 39→Reference Example 41→Reference Example 6→Example2.

TLC: Rf 0.29 (AcOEt:hexane:AcOH=5:14:1); NMR (DMSO-d₆): δ 12.87 (1H,brs), 9.53 (1H, brs), 7.83 (2H, d, J=8.5 Hz), 7.78-7.50 (5H, m), 7.39(2H, d, J=8.0 Hz), 6.86 (2H, d, J=8.0 Hz), 6.57 (1H, d, J=2.0 Hz), 6.50(1H, dd, J=8, 2 Hz), 4.82 (2H, brs), 2.44 (2H, q, J=7.5 Hz), 1.08 (3H,t, J=7.5 Hz).

EXAMPLE 42 4-(2-Phenylsulfonylamino-5-hydroxymethylphenoxymethyl)benzoicAcid

By using methyl 4-nitro-3-hydroxybenzoate, the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 19→Reference Example 20→Reference Example 2→Reference Example43→Reference Example 39→Reference Example 23→Reference Example 6→Example2.

TLC: Rf 0.39 (AcOEt:hexane:AcOH=13:6:1); NMR (DMSO-d₆): δ 12.83 (1H,brs), 9.56 (1H, s), 7.83 (2H, d, J=8.5 Hz), 7.78-7.50 (5H, m), 7.38 (2H,d, J=8.5 Hz), 6.88 (1H, d, J=8.0 Hz), 6.74 (1H, s), 6.56 (1H, d, J=8.0Hz), 5.10 (1H, brt, J=5.5 Hz), 4.83 (2H, s), 4.34 (2H, d, J=5.5 Hz).

REFERENCE EXAMPLE 46 Methyl 4-Chloro-2-hydroxybenzoate

To a solution of 4-chloro-2-hydroxybenzoic acid (5.0 g) in ether (50ml), diazomethane in ether was added until the reaction was terminatedat 0° C. The reaction mixture was concentrated under the reducedpressure. The residue was purified on silica gel column chromatography(hexane:AcOEt=4:1) to give the title compound (5.4 g) having thefollowing physical data.

TLC: Rf 0.60 (hexane:AcOEt=2:1).

REFERENCE EXAMPLE 47 2-Hydroxymethyl-5-chlorophenol

To a solution of lithium aluminum hydride (1.1 g) in THF (50 ml), methyl4-chloro-2-hydroxybenzoate (5.38 g; prepared in Reference Example 46.)in THF (50 ml) was added dropwise in a stream of argon at 0° C. Afterthe solution was warmed to at room temperature, the solution was stirredfor 30 minutes. To the reaction mixture, water was added. The mixturewas extracted with mixture solution of ether-AcOEt, washed, dried overand concentrated under the reduced pressure. The residue wasrecrystallized from mixture solution of hexane-AcOEt to give the titlecompound (3.92 g) having the following physical data.

TLC: Rf 0.60 (hexane:AcOEt=1:1).

REFERENCE EXAMPLE 48 Methyl4-(2-Mesyloxymethyl-5-chlorophenoxymethyl)benzoate

By using 2-hydroxymethyl-5-chlorophenol (prepared in Reference Example47.), the title compound having the following physical data was obtainedby the same procedure as Reference Example 6→Reference Example 8.

TLC: Rf 0.60 (benzene:acetone=9:1).

REFERENCE EXAMPLE 49 Methyl4-(2-Azidomethyl-5-chlorophenoxymethyl)benzoate

To a solution of methyl4-(2-mesyloxymethyl-5-chlorophenoxymethyl)benzoate (628 mg; prepared inReference Example 48.) in DMF (5.0 ml), sodium azide (530 mg) was addedin a stream of argon. The mixture was stirred for 40 minutes at 60° C.The reaction mixture was diluted with ethyl acetate. The impurity wasfiltered with celite. The filtrate was washed, dried over andconcentrated under the reduced pressure. The residue was purified onsilica gel column chromatography (hexane:AcOEt =10:1) to give the titlecompound (404 mg) having the following physical data.

TLC: Rf 0.56 (hexane:AcOEt=4:1).

REFERENCE EXAMPLE 50 Methyl4-(2-Aminomethyl-5-chlorophenoxymethyl)benzoate

To a solution of methyl 4-(2-azidomethyl-5-chlorophenoxymethyl)benzoate(389 mg; prepared in Reference Example 49.) in THF (4.0 ml),triphenylphosphine (462 mg) was added at room temperature. The mixturewas stirred for 3 hours. After stirring, water was added thereto. Themixture was stirred for 15 hours. The reaction mixture was concentratedunder the reduced pressure. The residue was purified on silica gelcolumn chromatography (CHCl₃:MeOH=50:1→10:1) to give the title compound(339 mg) having the following physical data.

TLC: Rf 0.22 (CHCl₃:MeOH=10:1).

EXAMPLE 43 4-(2-Phenylsulfonylaminomethyl-5-chlorophenoxymethyl)benzoicAcid

By using methyl 4-(2-aminomethyl-5-chlorophenoxymethyl)benzoate(prepared in Reference Example 50.), the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 2→Example 2.

TLC: Rf 0.49 (CHCl₃:MeOH AcOH=100:5:1); NMR (DMSO-d₆): δ 7.94 (2H, d,J=8.0 Hz), 7.77 (2H, m), 7.45-7.70 (5H, m), 7.25 (1H, d, J=8.2 Hz), 7.05(1H, d, J=1.8 Hz), 6.94 (1H, dd, J=1.8, 8.2 Hz), 5.20 (2H, s), 4.00 (2H,s).

EXAMPLE 444-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]phenylpropiolicAcid

By using4-[2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicacid (prepared in Example 18 (9).), the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 13→Reference Example 14→Reference Example 15∝Example 2.

TLC: Rf 0.32 (CHCl₃:MeOH=8:2); NMR: δ 7.80 (2H, d, J=8 Hz), 7.64 (2H, d,J=8 Hz), 7.68-7.26 (8H, m), 5.09 (2H, s), 4.38 (1H, sept, J=6.5 Hz),1.04 (6H, d,J=6.5 Hz).

EXAMPLE 454-[2-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenyl]ethyl]benzoicAcid

By using methyl4-[2-(2-t-butoxycarbonylamino-5-trifluoromethylphenyl)-(EZ)-vinyl]benzoate,the title compound having the following physical data was obtained bythe same procedure as Reference Example 20→Reference Example23→Reference Example 2→Example 17→Example 2.

TLC: Rf 0.46 (CHCl₃:MeOH=9:1); NMR: δ 8.09 (2H, d, J=8.2 Hz), 7.8-7.7(2H, m), 7.7-7.3 (7H, m), 6.88 (1H, d, J=8.2 Hz), 4.7-4.5 (1H, m),3.4-3.1 (2H, m), 3.1-2.9 (2H, m), 1.03 (3H, d, J=6.8 Hz), 0.93 (3H, d,J=6.8 Hz).

EXAMPLE 46 4-(2-Phenylsulfonylamino-4-chlorophenoxymethyl)benzyl Alcohol

By using methyl 4-(2-phenylsulfonylamino-4-chlorophenoxymethyl)benzoate(prepared in Example 7 (a).), the title compound having the followingphysical data was obtained by the same procedure as Reference Example43.

TLC: Rf 0.24 (hexane:AcOEt=1:1); NMR: δ7.75 (2H, m), 7.60 (1H, d, J=2.4Hz), 7.55 (1H, m), 7.45 (2H, m), 7.36 (2H, d, J=8.0 Hz), 7.13 (2H, d,J=8.0 Hz), 7.03 (1H, brs), 6.96 (1H, dd, J=2.4, 8.8 Hz), 6.68 (1H, d,J=8.8 Hz), 4.86 (2H, s), 4.73 (2H, d, J=5.8 Hz), 1.74 (1H, t, J=5.8 Hz).

EXAMPLE 474-[N-[2-(4-Chlorophenylsulfonylamino)-5-chlorophenyl]aminosulfonyl]benzoicAcid

By using 2-nitro-4-chloroaniline, the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 2→Reference Example 1 2→Reference Example 2→Example 2.

TLC: Rf 0.22 (CHCl₃:MeOH:H₂O=8:2:0.2); NMR (DMSO-d₆): δ 9.68 (1H, br),8.11 (2H, d, J=8.4 Hz), 7.84 (2H, d, J=8.4 Hz), 7.69 (2H, d, J=8.8 Hz),7.62 (2H, d, J=8.8 Hz), 7.12 (1H, dd, J=2.4 and 8.4 Hz), 7.02 (1H, d,J=2.4 Hz), 6.97 (1H, d, J=8.4 Hz).

EXAMPLE 484-[2-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenyl]-(E)-vinyl]benzoicAcid

By using methyl4-[2-(2-t-butoxycarbonylamino-5-trifluoromethylphenyl)-(E)-vinyl]benzoate,the title compound having the following physical data was obtained bythe same procedure as Reference Example 23→Reference Example 2→Example17→Example 2.

TLC: Rf 0.45 (CHCl₃:MeOH=9:1); NMR: δ 8.2-8.0 (3H, m), 7.9-7.7 (2H, m),7.6-7.4 (7H, m), 7.2-7.0 (2H, m), 4.8-4.6 (1H, m), 1.08 (3H, d, J=5.0Hz), 1.05 (3H, d, J=5.0 Hz).

EXAMPLE 48(1)4-[2-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenyl]-(Z)-vinyl]benzoicAcid

By using methyl4-[2-(2-t-butoxycarbonylamino-5-trifluoromethylphenyl)-(Z)-vinyl]benzoate,the title compound having the following physical data was obtained bythe same procedure as Reference Example 23→Reference Example 2→Example17→Example 2.

TLC: Rf 0.51 (CHCl₃:MeOH=9:1); NMR: δ 7.97 (2H, d, J=8.4 Hz), 7.9-7.7(2H, m), 7.7-7.4 (5H, m), 7.31 (2H, d, J=8.4 Hz), 7.1-6.9 (2H, m), 6.77(1H, d, J=12.4 Hz), 4.7-4.5 (1H, m), 1.19 (3H, d, J=6.6 Hz), 1.04 (3H,d, J=6.6 Hz).

EXAMPLE 49 4-(2-Benzoylamino-5-chlorophenoxymethyl)benzoic Acid

By using 2-nitro-5-chlorophenol, the title compound having the followingphysical data was obtained by the same procedure as Reference Example6→Reference Example 12→Example 11 →Example 2.

TLC: Rf 0.51 (CHCl₃:MeOH AcOH=100:5:1); NMR (DMSO-d₆): δ 12.92 (1H,brs), 9.64 (1H, s), 7.94 (4H, m), 7.75 (1H, d, J=8.6 Hz), 7.47-7.68 (5H,m), 7.23 (1H, d, J=2.2 Hz), 7.05 (1H, dd, J=2.2, 8.6 Hz), 5.32 (2H, s).

EXAMPLE 50-50(2)

By using 4-(2-phenylsulfonylamino-5-isopropylphenoxymethyl)benzoic acid(prepared in Example 40.) or4-(2-phenylsulfonylamino-5-ethylphenoxymethyl)benzoic acid (prepared inExample 41.), the title compounds having the following physical datawere obtained by the same procedure as Reference Example 1 →Example17→Example 2.

EXAMPLE 504-[2-(N-Isopropyl-phenylsulfonylamino)-5-isopropylphenoxymethyl]benzoicAcid

TLC: Rf 0.13 (CHCl₃:MeOH=19:1); NMR (DMSO-d₆): δ 7.85 (2H, d, J=8 Hz),7.79-7.52(5H, m), 7.40 (2H, d, J=8 Hz), 7.01 (1H, d, J=8 Hz), 6.73 (1H,d, J=2 Hz), 6.65 (1H, dd, J=8 and 2 Hz), 4.83 (2H, brs), 4.47 (1H, m),2.80 (1H, m), 1.1 4 (6H, d, J=7 Hz), 0.95 (6H, d, J=7 Hz).

EXAMPLE 50(1)4-[2-(N-Methylphenylsulfonylamino)-5-isopropylphenoxymethyl]benzoic Acid

TLC: Rf 0.13 (CHCl₃:MeOH=19:1); NMR (DMSO-d₆): δ 7.85 (2H, d, J=8 Hz),7.76-7.53 (5H, m), 7.39 (2H, d, J=8 Hz), 6.98 (1H, d, J=8 Hz), 6.77 (1H,d, J=2 Hz), 6.70 (1H, dd, J=8 and 2 Hz), 4.78 (2H, brs), 3.33 (3H, s),2.82 (1H, m), 1.15 (6H, d, J=7 Hz).

EXAMPLE 50(2)4-[2-(N-Isopropyl-phenylsulfonylamino)-5-ethylphenoxymethyl]benzoic Acid

TLC: Rf 0.40 (AcOEt:hexane:ACOH=5:14:1); NMR: δ 7.97 (2H, d, J=8.0 Hz),7.82-7.70 (2H, m), 7.62-7.32 (5H, m), 7.05 (1H, d, J=8.0 Hz), 6.60 (1H,dd, J=8, 1.5 Hz), 6.53 (1H, d, J=1.5 Hz), 4.86 (2H, brs), 4.36 (1H, qn,J=6.0 Hz), 2.55 (2H, q, J=7.5 Hz), 1.18 (3H, t, J=7.5 Hz), 1.02 (6H,brd, J=6.0 Hz).

EXAMPLE 514-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid·Sodium Salt

To a solution of4-[2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid (425 mg; prepared in Example 18(40).) in MeOH.(5 ml), 2N NaOH (0.41ml) was added. The mixture was stirred at room temperature. The mixturewas distilled off azeotropically with benzene three times to give thetitle compound (430 mg) having the following physical data.

TLC: Rf 0.19 (hexane:AcOEt=1:1); NMR: δ 7.60 (2H, d, J=7 Hz), 7.40-6.97(11H, m), 6.47 (1H, d, J=1 6 Hz), 4.62 (2H, bs), 4.20-4.08 (1H, m), 0.77(6H, d, J=5 Hz).

EXAMPLE 52(1)-52(5)

By using methyl 4-(2-amino-5-trifluoromethylphenoxymethyl)benzoate(prepared in Reference Example 17.) and the correspondingbenzenesulfonylchloride derivatives, the title compounds having thefollowing physical data were obtained by the same procedure as Example4→Example 19 (isopropanol was used instead ofcyclopentylmethanol.)→Example 2.

EXAMPLE 52(1)4-[2-(N-isopropyl-4-propoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.55 (CHCl₃:MeOH=9:1); NMR: δ 8.16 (2H, d, J=8.8 Hz), 7.71 (2H,d, J=8.8 Hz), 7.54 (2H, d, J=8.8 HZ), 7.30-7.22 (3H, m), 6.80 (2H, d,J=8.8 Hz), 5.14 (2H, s), 4.44-4.24 (1H, m), 3.92 (2H, t, J=6.6 Hz),1.91-1.72 (2H, m), 1.14-0.98 (9H, m).

EXAMPLE 52(2)4-[2-(N-Isopropyl-4-ethylthiophenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.64 (CHCl₃:MeOH=9:1); NMR: δ 8.17 (2H, d, J=8.4 Hz), 7.66 (2H,d, J=8.4 Hz), 7.53 (2H, d, J=8.4 Hz), 0.30-7.20 (3H, m), 7.16 (2H, d,J=8.4 Hz), 5.12 (2H, s), 4.44-4.22 (1H, m), 2.98 (2H, q, J=7.6 Hz), 1.36(3H, t, J=7.6 Hz), 1.09 (3H, d, J=6.6 Hz), 1.05 (3H, d, J=6.6 Hz).

EXAMPLE 52(3)4-[2-(N-Isopropyl-4-methylthiophenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.56 (CHCl₃:MeOH=9:1); NMR: δ 8.16 (2H, d, J=8.4 Hz), 7.67 (2H,d, J=8.4 Hz), 7.52 (2H, d, J=8.4 Hz), 7.30-7.20 (3H, m), 7.12 (2H, d,J=8.4 Hz), 5.12 (2H, s), 4.46-4.24 (1H, m), 2.48 (3H, s), 1.09 (3H, d,J=7.0 Hz), 1.05 (3H, d, J=7.0 Hz).

EXAMPLE 52(4)4-[2-(N-Isopropyl-4-butoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.51 (CHCl₃:MeOH 9:1); NMR: δ 8.16 (2H, d, J=8.4 Hz), 7.71 (2H,d, J=8.8 Hz), 7.54 (2H, d, J=8.4 Hz), 7.30-7.22 (3H, m), 6.79 (2H, d,J=8.8 Hz), 5.14 (2H, s), 4.42-4.27 (1H, m), 3.96 (2H, t, J=6.2 Hz),1.87-1.70 (2H, m), 1.60-1.40 (2H, m), 1.14-0.92 (9H, m).

EXAMPLE 52(5)4-[2-(N-Isopropyl-4-isopropoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.68 (CHCl₃:MeOH=9:1); NMR: δ 8.17 (2H, d, J=8.0 Hz), 7.71 (2H,d, J=8.8 Hz), 7.56 (2H, d, J=8.0 Hz), 7.30-7.22 (3H, m), 6.78 (2H, d,J=8.8 Hz), 5.15 (2H, s), 4.62-4.50 (1H, m), 4,40-4.23 (1H, m), 1.35 (6H,d, J=5.8 Hz), 1.08 (3H, d, J=7.4 Hz), 1.04 (3H, d, J=7.4 Hz).

EXAMPLE 53(1)-53(3)

By using methyl 4-(2-amino-5-chlorophenoxymethyl)benzoate (prepared inReference Example 7.) or methyl4-(2-amino-5-trifluoromethylphenoxymethyl)benzoate (prepared inReference Example 17.), the title compounds having the followingphysical data were obtained by the same procedure as Example 27 (thecorresponding aldehyde was used.)→Example 11→Example 2.

EXAMPLE 53(1)4-[2-(N-Isobutyl-benzoylamino)-5-chlorophenoxymethyl]benzoic acid

TLC: Rf 0.53 (CHCl₃:MeOH=5:1); NMR(CDCl₃+1 drop of CD₃OD): δ 8.08 (2H,d, J=8 Hz), 7.44-7.04 (8H, m), 6.94-6.80 (1H, m), 6.73 (1H, s), 5.03(1H, d, J=13 Hz), 4.82 (1H, d, J=13 Hz), 3.91 (1H, dd, J=15, 7 Hz), 3.49(1H, dd, J=15, 7 Hz), 2.10-1.60 (1H, m), 0.98 (6H, d, J=7 Hz).

EXAMPLE 53(2)4-[2-(N-Isopropyl-benzoylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 8.18 (2H, d, J=8.4 Hz), 7.52-7.35(3H, m), 7.30-7.03 (6H, m), 7.02-6.92 (1H, m), 5.20-4.90 (2H, m),4.90-4.70 (1H, m), 1.50-1.00 (6H, m).

EXAMPLE 53(3)4-[2-(N-Isopropyl-2-furoylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

TLC: Rf 0.43 (CHCl₃:MeOH=9:1); NMR: δ 8.09 (2H, d, J=7.8 Hz), 7.43-7.22(5H, m), 7.15 (1H, s), 6.25-6.20 (1H, m), 6.16-6.08 (1H, br), 5.20-4.84(3H, m), 1.40-1.00 (6H, m).

EXAMPLE 54 4-(2-Benzoylamino-5-chlorobenzoylamino)benzoic Acid

By using 2-nitro-5-chlorobenzoic acid chloride (prepared in ReferenceExample 13.), the title compound having the following physical data wasobtained by the same procedure as Example 11→Reference Example10→Example 11→Example 2.

TLC: Rf 0.52 (AcOEt:hexane:AcOH=7:12:1); NMR (DMSO-d₆): δ 12.77 (1H,brs), 11.33 (1H, s), 10.85 (1H, s), 8.36 (1H, d, J=9.0 Hz), 8.02-7.78(7H, m), 7.69 (1H, dd, J=9.0, 2.5 Hz), 7.64-7.48 (3H, m).

EXAMPLE 55(1)-55(2)

By using 2-nitro-5-chlorobenzoic acid chloride (prepared in ReferenceExample 13.), the title compounds having the following physical datawere obtained by the same procedure as Example 11→Reference Example10→Reference Example 2→Example 2.

EXAMPLE 55(1) 4-[2-(2-Thienylsulfonylamino)-5-chlorobenzoylamino]benzoicAcid

TLC: Rf 0.18 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.73 (1H, br), 10.68(1H, brs), 10.48 (1H, brs), 7.93 (2H, d, J=8.8 Hz), 7.87 (1H, dd, J=1.2and 3.6 Hz), 7.81 (1H, d, J=2.2 Hz), 7.76 (2H, d, J=8.8 Hz), 7.61-7.53(2H, m), 7.41 (1H, d, J=8.8 Hz), 7.05 (1H, dd, J=3.8 and 4.0 Hz).

EXAMPLE 55(2) 4-(2-Butylsulfonylamino-5-chlorobenzoylamino)benzoic acid

TLC: Rf 0.26 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 12.77 (1H, brs), 10.80(1H, brs), 9.94 (1H, s), 7.93 (2H, d, J=8.8 Hz), 7.88 (1H, d, J=2.2 Hz),7.82 (2H, d, J=8.8 Hz), 7.61 (1H, dd, J=793 (2H, d, 8.8 Hz), 7.54 (1H,d, J=8.8 Hz), 3.18 (2H, t-like), 1.66-1.51 (2H, m), 1.37-1.19 (2H, m),0.74 (3H, t, J=7.2 Hz).

REFERENCE EXAMPLE 51 Methyl 4-(2-Nitro-5-methylphenylthiomethyl)benzoate

To a solution of methyl 4-acetylthiomethylbenzoate (794 mg) in MeOH (5.0ml), sodium methoxide (191 mg) and 3-fluoro-4-nitrotoluene (500 mg) wereadded suceedingly in a stream of argon at 0° C. The mixture was warmedslowly to become at room temperature. The mixture was stirred for 4hours. To the reaction mixture, a saturated aqueous ammonium chloridewas added. The mixture was extracted with ethyl acetate, washed, driedover and concentrated under the reduced pressure. The residue wasrecrystrallized from ethanol to give the title compound (646 mg) havingthe following physical data.

TLC: Rf 0.49 (hexane: CH₂Cl₂:AcOEt=8:4:1).

EXAMPLE 564-[2-(N-Isopropyl-2-furanylsulfonylamino)-5-methylphenylthiomethyl]benzoicAcid

By using methyl 4-(2-nitro-5-methylphenylthiomethyl)benzoate (preparedin Reference Example 51.), the title compound having the followingphysical data was obtained by the same procedure as Reference Example11→Reference Example 2→Example 17→Example 2.

TLC: Rf 0.45 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.04 (2H, d, J=8.4 Hz),7.58 (1H, dd, J=0.8, 1.8 Hz), 7.48 (2H, d, J=8.4 Hz), 7.08 (1H, m),6.91-6.98 (2H, m), 6.84 (1H, d, J=8.0 Hz), 6.50 (1H, dd, J=2.0, 3.8 Hz),4.47 (1H, sept, J=6.8 Hz), 4.19 (2H, s), 2.28 (3H, s), 1.16 (3H, d,J=6.8 Hz), 1.06 (3H, d, J=6.8 Hz).

EXAMPLE 574-[2-(N-Isobutyl-2-thienylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

By using 2-nitro-5-trifluoromethylphenol, the title compound having thefollowing physical data was obtained by the same procedure as ReferenceExample 18(b)→Reference Example 12→Reference Example 2→Example17→Example 2.

TLC: Rf 0.51 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 7.80 (1H, d, J=16.2 Hz),7.57 (2H, d, J=8.0 Hz), 7.22-7.46 (6H, m), 7.16 (1H, m), 6.93 (1H, dd,J=4.0, 5.2 Hz), 6.49 (1H, d, J=16.2 Hz), 4.94 (2H, brs), 3.45 (2H, d,J=7.2 Hz), 1.62 (1H, m), 0.91 (6H, d, J=6.6 Hz).

EXAMPLE 586-[2-(N-Isopropyl-phenylsulfonylamino)-5-trifluoromethylphenoxymethyl]-2-naphthalicAcid

By using 2-(N-isopropyl-phenylsulfonylamino)-5-trifluoromethylphenol(prepared in Reference Example 24.) and ethyl6-hydroxymethyl-2-naphthate, the title compound having the followingphysical data was obtained by the same procedure as Reference Example18(b)→Example 2.

TLC: Rf 0.55 (CHCl₃:MeOH:AcOH=100:5:1); NMR: δ 8.74 (1H, s), 8.17 (1H,dd, J=1.8, 8.8 Hz), 8.03 (1H, d, J=8.4 Hz), 8.03 (1H, brs), 7.95 (1H, d,J=8.8 Hz), 7.79-7.87 (2H, m), 7.61 (1H, dd, J=1.4, 8.4 Hz), 7.43 (1H,m), 7.32 (3H, m), 7.26 (2H, m), 5.26 (2H, s), 4.39 (1 H, m), 1.08 (3H,d, J=6.6 Hz), 1.06 (3H, d, J=6.6 Hz).

EXAMPLE 59(1)-59(3)

By using 2-nitro-5-trifluoromethylphenol, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 18(b)→Reference Example 12→Example 27→Example 11→Example 2.

EXAMPLE 59(1)4-[2-(N-Isopropyl-2-furoylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.44 (CHCl₃:MeOH=9:1); NMR: δ 7.76 (1H, d, J=16.2 Hz), 7.52 (2H,d, J=8.4 Hz), 7.38 (1H, d, J=8.4 Hz), 7.32 (1H, d, J=8.4 Hz), 7.28-7.20(3H, m), 7.17 (1H, s), 6.45 (1H, d, J=16.2 Hz), 6.24-6.19 (1H, m),6.11-6.00 (1H, br), 5.20-4.80 (3H, m), 1.40-1.00 (6H, m).

EXAMPLE 59(2)4-[2-(N-Isobutyl-2-furoylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.49 (CHCl₃:MeOH=9:1); NMR: δ 7.76 (1H, d, J=1 5.9 Hz), 7.52(2H, d, J=8.4 Hz), 7.39 (1H, d, J=8.1 Hz), 7.33-7.15 (5H, m), 6.45 (1H,d, J=15.9 Hz), 6.28-6.10 (2H, m), 5.20-4.90 (2H, m), 4.00-3.80 (1H, br),3.60-3.30 (1H, br), 2.00-1.80 (1H, m), 0.95 (6H, d, J=6.6 Hz).

EXAMPLE 59(3)4-[2-(N-Isopropyl-butyrylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.42 (CHCl₃:MeOH=9:1); NMR: δ 7.78 (1H, d, J=15.9 Hz), 7.58 (2H,d, J=8.1 Hz), 7.42 (2H, d, J=8.1 Hz), 7.35-7.20 (3H, m), 6.48 (1H, d,J=15.9 Hz), 5.20-4.93 (3H, m), 1.90 (2H, dt, J=2.7, 7.5 Hz), 1.64-1.50(2H, m), 1.17 (3H, d, J=6.6 Hz), 0.94 (3H, d, J=6.6 Hz), 0.79 (3H, t,J=7.2 Hz).

EXAMPLE 60(1)-60(2)

By using 2-nitro-5-trifluoromethylphenol, the title compounds having thefollowing physical data were obtained by the same procedure as ReferenceExample 18(b)→Reference Example 12→Reference Example 2→Example19→Example 2.

EXAMPLE 60(1)4-[2-(N-Isopropyl-4-ethoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.51 (CHCl₃:MeOH=9:1); NMR: δ 7.82 (1H, d, J=16.0 Hz), 7.72 (2H,d, J=8.8 Hz), 7.61 (2H, d, J=8.6 Hz), 7.48 (2H, d, J=8.6 Hz), 7.28-7.22(3H, m), 6.77 (2H, d, J=8.8 Hz), 6.50 (1H, d, J=16.0 Hz), 5.10 (2H, s),4.40-4.20 (1H, m), 4.01 (2H, q, J=6.8 Hz), 1.43 (3H, t, J=6.8 Hz), 1.07(3H, d, J=6.6 Hz), 1.03 (3H, d, J=6.6 Hz).

EXAMPLE 60(2)4-[2-(N-Isobutyl-4-ethoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicAcid

TLC: Rf 0.57 (CHCl₃:MeOH=9:1); NMR: δ 7.81 (1H, d, J=1 5.6 Hz),7.60-7.47 (3H, m), 7.44 (1H, d, J=8.2 Hz), 7.30-7.10 (5H, m), 6.73(2H,d, J=8.8 Hz), 6.50 (1H, d, J=15.6 Hz), 5.00-4.80 (2H, br), 3.95 (2H, q,J=7.0 Hz), 3.39 (2H, d, J=6.8 Hz), 1.70-1.50 (1H, m), 1.41 (3H, t, J=6.8Hz), 0.88 (6H, d, J=6.6 Hz).

EXAMPLE 614-[2-(N-Isopropyl-3-ethoxyphenylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicAcid

By using methyl 4-(2-amino-5-trifluoromethylphenoxymethyl)benzoate(prepared in Reference Example 17.), the title compound having thefollowing physical data was obtained by the same procedure as Example4→Example 19→Example 2.

TLC: Rf 0.63 (CHCl₃:MeOH=9:1); NMR: δ 8.15 (2H, d, J=8.4 Hz), 7.53 (2H,d, J=8.4 Hz), 7.40-7.20 (6H, m), 7.02 (1H, ddd, J=1.2, 2.4, 8.0 Hz),5.13 (2H, s), 4.52-4.36 (1H, m), 3.98 (2H, q, J=6.8 Hz), 1.40 (3H, t,J=6.8 Hz), 1.08 (3H, d, J=6.6 Hz), 1.06 (3H, d, J=6.6 Hz).

EXAMPLE 62(1)-62(2)

By using 2-nitrobenzoic acid chloride, the title compounds having thefollowing physical data were obtained by the same procedure as Example11→Reference Example 20→Reference Example 2→Example 2.

EXAMPLE 62(1) 4-[2-(3-Chlorophenylsulfonylamino)benzoylamino]benzoicAcid

TLC: Rf 0.38 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 10.59 (1H, s), 10.44(1H, s), 7.95 (2H, d, J=8.4 Hz), 7.86-7.60 (6H, m), 7.58-7.45 (2H, m),7.38-7.25 (2H, m).

EXAMPLE 62(2) 4-[2-(4-Bromophenylsulfonylamino)benzoylamino]benzoic Acid

TLC: Rf 0.39 (CHCl₃:MeOH=9:1); NMR (DMSO-d₆): δ 10.55 (1H, s), 10.38(1H, s), 7.96 (2H, d, J=8.8 Hz), 7.90-7.45 (8H, m), 7.44-7.25 (2H, m).

FORMULATION EXAMPLE 1

The following compounds were admixed in conventional method and punchedout to obtain 100 tablets each containing 5 mg of active ingredient.

4-(2-phenylsulfonylamino-5-chlorobenzoylamino)benzoic acid 500 mg(prepared in Example 2.) Cellulose calcium glycolate (disintegratingagent) 200 mg Magnesium stearate (lubricating agent) 100 mg Microcrystalline cellulose 9.2 g

We claim:
 1. A sulfonamide or carbonamide derivative of the formula (I)

(wherein

each, independently, is a C5-15 carbocyclic ring, Z¹ is —COR¹, —C1-4alkylene-COR¹, —CH═CH—COR¹, —C≡COR¹, or —O—C1-3 alkylene-COR¹, (wherein,R¹ is hydroxy, C1-4 alkoxy or formula NR⁶R⁷ (wherein, R⁶ and R⁷ each,independently, is H or C1-4 alkyl), or —C1-5 alkylene-OH, Z² is H, C1-4alkyl, C1-4 alkoxy, nitro, halogen, trifluoromethyl, trifluoromethoxy,hydroxy or COR¹ (wherein R¹ is as defined hereinbefore)), Z³ is singlebond or C1-4 alkylene, Z⁴is SO₂or CO, Z⁵ is (1) C1-8 alkyl, C2-8alkenyl, or C2-8 alkynyl, (2) phenyl, C3-7 cycloalkyl, or 5-7 memberedheterocyclic ring containing one or two oxygen, sulfur or nitrogenatom(s), or (3) C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl substituted byphenyl or C3-7 cycloalkyl (phenyl, C3-7 cycloalkyl and 5-7 memberedheterocyclic ring containing one or two oxygen, sulfur or nitrogenatom(s) mentioned in the above (2) and (3) may be substituted by 1-5 ofR⁵ (wherein R⁵ (if two or more R⁵, each independently) is H, C1-6 alkyl,C1-6 alkoxy, C1-6 alkylthio, nitro, halogen trifluoromethyl,trifluoromethoxy or hydroxy)), R² is alkoxy or C(O)NH, R³ is H, C1-6alkyl, C1-6 alkoxy, C1-6 alkylthio, nitro, halogen, trifluoromethyl,trifluoromethoxy, hydroxy or hydroxymethyl, R⁴is (1) H, (2) C1-18 alkyl,C2-8 alkenyl, or C2-8 alkynyl, (3) C1-6 alkyl substituted by one or twosubstituent(s) selected from the group consisting of COOZ⁸, CONZ⁹Z⁰, andOZ⁸ (wherein Z⁸, Z⁹ and Z¹⁰ each, independently, is H or C1-4 alkyl) andC1-4 alkoxy-C1-4 alkoxy, (4) C3-7 cycloalkyl, or (5) C1-4 alkyl, C2-4alkenyl or C2-4 alkynyl substituted by phenyl or C3-7 cycloalkyl (phenyland C3-7 cycloalkyl mentioned in the above (4) and (5) may besubstituted by 1-5 of R⁵ (wherein R⁵ is as defined hereinbefore)), and nand t each, independently, is an integer of 1-4, with the proviso that(1) R² and Z³ should be connected at the 1- or 2-position of

(2) when

 is a benzene ring and (Z²)t is other than COR¹, Z¹ should be connectedat the 3- or 4-position of the benzene ring and (3) the compoundswherein

are excluded, or a non-toxic salt thereof.
 2. A compound according toclaim 1, wherein at least one of

and Z⁵ is 5-7 membered heterocyclic ring containing one or two oxygen,sulfur or nitrogen atom(s).
 3. A compound according to claim 1, wherein

is C5-15 carbocyclic ring and Z⁵ is 5-7 membered heterocyclic ringcontaining one or two oxygen, sulfur or nitrogen atom(s).
 4. A compoundaccording to claim 1, wherein R² is O, S, NZ⁶ (wherein Z⁶ is H or C1-4alkyl.), Z⁷—C1-4 alkylene, C1-4 alkylene-Z⁷, or C1-3 alkylene-Z⁷—C1-3alkylene (wherein each Z⁷ is O, S or NZ⁶ (wherein Z⁶ is as definedhereinbefore.).).
 5. A compound according to claim 1, wherein R² is CO,CO—C1-4 alkylene, C1-4 alkylene-CO or C1-3 alkylene-CO—C1-3 alkylene. 6.A compound according to claim 1 which is selected from (1)4-[2-(N-isopropyl-2-thienylsulfonylamino)-5-chlorophenoxymethyl]benzoicacid, (2)4-[2-(N-isopropyl-2-thienylsulfonylamino)-5-methylphenoxymethyl]benzoicacid, (3)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]benzoicacid, (4)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]benzoicacid, (5)4-[2-(N-propyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid, (6)4-[2-(N-propyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]benzoicacid, (7)4-[2-(N-isobutyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]benzoicacid, (8)4-[2-(N-isobutyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid, (9)4-[2-[N-(prop-2-enyl)-2-furanylsulfonylamino]-5-methylphenoxymethyl]benzoicacid, (10)4-[2-[N-(2-methylprop-2-enyl)-2-furanylsulfonylamino]-5-methylphenoxymethyl]benzoicacid, (11)4-[2-(N-isobutyl-2-furanylsulfonylamino)-4-methylphenoxymethyl]benzoicacid, (12)4-[2-(N-isopropyl-2-furanylsulfonylamino)-4-methylphenoxymethyl]benzoicacid, (13)4-[2-[N-(2-methylprop-2-enyl)-2-furanylsulfonylamino]-4-methylphenoxymethyl]benzoicacid, (14)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-methylphenoxymethyl]cinnamicacid, (15)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid, (16)4-[2-(N-isopropyl-2-furanylsulfonylamino)-4-trifluoromethylphenoxymethyl]benzoicacid, (17)4-[2-(N-isobutyl-2-furanylsulfonylamino)-4-trifluoromethylphenoxymethyl]benzoicacid, (18)4-[2-(N-isobutyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]benzoicacid, (19)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]cinnamicacid, (20)4-[2-(N-isobutyl-2-furanylsulfonylamino)-5-chlorophenoxymethyl]cinnamicacid, (21)4-[2-(N-isobutyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicacid, (22)4-[2-(N-isobutyl-2-furanylsulfonylamino)-4-chlorophenoxymethyl]benzoicacid, (23)4-[2-(N-isobutyl-2-furanylsulfonylamino)-4-methylphenoxymethyl]cinnamicacid, (24)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicacid, (25)4-[2-(N-isopropyl-2-thienylsulfonylamino)-5-trifluoromethylphenoxymethyl]benzoicacid, (26)4-[2-[N-(2-hydroxy-2-methylpropyl)-2-thienylsulfonylamino]-5-trifluoromethylphenoxymethyl]benzoicacid, (27)4-[2-(N-isopropyl-2-furoylamino)-5-trifluoromethylphenoxymethyl]benzoicacid, (28) 4-[2-(2-thienylsulfonylamino)-5-chlorobenzoylamino]benzoicacid, (29)4-[2-(N-isopropyl-2-furanylsulfonylamino)-5-methylphenylthiomethyl]benzoicacid, (30)4-[2-(N-isobutyl-2-thienylsulfonylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid, (31)4-[2-(N-isopropyl-2-furoylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid and (32)4-[2-(N-isobutyl-2-furoylamino)-5-trifluoromethylphenoxymethyl]cinnamicacid, and methyl esters thereof.
 7. A prostaglandin E₂ antagonist oragonist which comprises the sulfonamide or carboamide derivative of theformula (I) depicted in claim 1 or a non-toxic salt thereof as an activeingredient.